gender reassignment medications

Practical Guidelines for Transgender Hormone Treatment

Adapted from:  Gardner,   Ivy  and  Safer, Joshua D . 2013   Progress on the road to better medical care for transgender patients. Current Opinion in Endocrinology, Diabetes and Obesity 20(6): 553-558.

• In order to improve transgender individuals’ access to health care, the approach to transgender medicine needs to be generalized and accessible to physicians in multiple specialties.
• A practical target for hormone therapy for transgender men (FTM) is to increase testosterone levels to the normal male physiological range (300–1000 ng/dl) by administering testosterone.
• A practical target for hormone therapy for transgender women (MTF) is to decrease testosterone levels to the normal female range (30–100 ng/dl) without supra- physiological levels of estradiol (<200 pg/ml) by administering an antiandrogen and estrogen.
• Transgender adolescents usually have stable gender identities and can be given GnRH analogs to suppress puberty until they can proceed with hormone therapy as early as age 16.

Hormone regimes for transgender men (female to men, FTM)

    1. Oral

• Testosterone undecanoate*      160–240mg/day

   2. Parenterally (i.m. or subcutaneous)

• Testosterone enanthate or cypionate      50–200mg/week or 100–200mg/2 weeks
• Testosterone undecanoate      1000 mg/12 weeks

   3. Transdermal

• Testosterone 1% gel      2.5 – 10 g/day
• Testosterone patch      2.5 – 7.5 mg/day 

i.m., intramuscular. *Not available in the USA.

Monitoring for transgender men (FTM) on hormone therapy:

• Monitor for virilizing and adverse effects every 3 months for first year and then every 6 – 12 months.
• Monitor serum testosterone at follow-up visits with a practical target in the male range (300 – 1000 ng/dl). Peak levels for patients taking parenteral testosterone can be measured 24 – 48 h after injection. Trough levels can be measured immediately before injection.
• Monitor hematocrit and lipid profile before starting hormones and at follow-up visits.
• Bone mineral density (BMD) screening before starting hormones for patients at risk for osteo- porosis. Otherwise, screening can start at age 60 or earlier if sex hormone levels are consistently low.
• FTM patients with cervixes or breasts should be screened appropriately.

Hormone regimes for transgender women (male to women, MTF)  

     1. Anti-androgen

• Spironolactone    100 – 200 mg/day (up to 400 mg)
• Cyproterone acetatea    50–100mg/day
• GnRH agonists    3.75 mg subcutaneous monthly

    2. Oral estrogen

• Oral conjugated estrogens    2.5–7.5mg/day
• Oral 17-beta estradiol    2–6mg/day

    3. Parenteral estrogen

• Estradiol valerate   5–20mg i.m./2 weeks   or cypionate   2–10mg i.m./week

    4. Transdermal estrogen

• Estradiol patch     0.1–0.4mg/2X week

i.m., Intramuscular; MTF, male to female. aNot available in the USA.

Monitoring for transgender women (MTF) on hormone therapy:

• Monitor for feminizing and adverse effects every 3 months for first year and then every 6– 12 months.
• Monitor serum testosterone and estradiol at follow-up visits with a practical target in the female range (testosterone 30 – 100 ng/dl; E2 <200 pg/ml).
• Monitor prolactin and triglycerides before start- ing hormones and at follow-up visits.
• Monitor potassium levels if the patient is taking spironolactone.
• BMD screening before starting hormones for patients at risk for osteoporosis. Otherwise, start screening at age 60 or earlier if sex hormone levels are consistently low.
• MTF patients should be screened for breast and prostate cancer appropriately.

3. Leinung MC, Urizar MF, Patel N, Sood SC. Endocrine treatment of transsexual  * persons: extensive personal experience. Endocr Pract 2013; 19:644 – 650.

4. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Is hormonal therapy associated *with better quality of life in transsexuals? A cross-sectional study. J Sex Med 2012; 9:531–541.

5. Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. J Am Med Assoc 2011; 306:971 – 977.

6. Safer JD, Tangpricha V. Out of the shadows: it is time to mainstream treatment for transgender patients. Endocrine Pract 2008; 14:248 – 250.

7. Reiner WG, Gearhart JP. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. N Engl J Med 2004; 350:333 – 341.

8. Meyer-Bahlburg HFL. Gender identity outcome in female-raised 46,XY per- sons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav 2005; 34:423 – 438.

9. Zhou J-N, Hofman MA, Gooren LJG, Swaab DF. A sex difference in the human brain and its relation to transsexuality. Nature 1995; 378:68 – 70.

10. Kruijver FP, Zhou JN, Pool CW, et al. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 2000; 85:2034 – 204z

11. Berglund H, Lindstro ̈ m P, Dhejne-Helmy C, Savic I. Male-to-female transsex- uals show sex-atypical hypothalamus activation when smelling odorous steroids. Cerebr Cortex 2008; 18:1900 – 1908.

12. Rametti G, Carrillo B, Go ́mez-Gil E, et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J Psychiatr Res 2011; 45:199 – 204.

13. RamettiG,CarrilloB,Go ́mez-GilE,etal.Themicrostructureofwhitematterin male to female transsexuals before cross-sex hormonal treatment. A DTI study. J Psychiatr Res 2011; 45:949–954.

14. GreenR,NewmanL,StollerR.Treatmentofboyhood‘transsexualism’.Arch Gen Psychiatry 1972; 26:213–217.

15. Liao L-M, Audi L, Magritte E, et al. Determinant factors of gender identity: a commentary. J Pediatr Urol 2012; 8:597–601.

16. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th ed.; 2011. http://www.wpath.org/documents/Standards%20of%20Care% 20V7%20-%202011%20WPATH.pdf (Accessed on 24 December 2012)

17. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endo- crine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009; 94:3132 – 3154.

18. Gooren LJ. Care of transsexual persons. N Engl J Med 2011; 364:2559– 2560.

19. BhasinS,SaferJ,TangprichaV.Thehormonefoundation’spatientguideto the endocrine treatment of transsexual persons. J Clin Endocrinol Metab 2009; 94:.

20. Bockting WO, Miner MH, Swinburne Romine RE, et al. Stigma, mental health, *  and resilience in an online sample of the US transgender population. Am J Public Health 2013; 103:943 – 951.

21. Olshan JS, Spack NP, Eimicke T, et al. Evaluation of the efficacy of sub-cutaneous administration of testosterone in female to male transexuals and hypogonadal males. Endocr Rev 2013; 34:(03_MeetingAbstracts): MON- 594.

22. Nagarajan V, Chamsi-Pasha M, Tang WHW. The role of aldosterone receptor antagonists in the management of heart failure: an update. Cleve Clin J Med 2012; 79:631 – 639.

23. Asscheman H, Giltay EJ, Megens JAJ, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 2011; 164:635 – 642.

24. Wierckx K, Mueller S, Weyers S, et al. Long-term evaluation of cross-sex * hormone treatment in transsexual persons. J Sex Med 2012; 9:2641–2651.

25. Wallien MSC, Cohen-Kettenis PT. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry 2008; 47:1413 – 1423. 26. Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJG. The treatment of adolescent transsexuals: changing insights. J Sex Med 2008; 5:1892–1897.

27. De Vries ALC, Steensma TD, Doreleijers TAH, Cohen-Kettenis PT. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med 2011; 8:2276 – 2283.

28. Safer JD, Pearce EN. A simple curriculum content change increased medical & student comfort with transgender medicine. Endocrine Pract 2013; 33:39–44.

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• Puberty blockers for transgender and gender-diverse youth

Puberty blockers can be used to delay the changes of puberty in transgender and gender-diverse youth who have started puberty. The medicines most often used for this purpose are called gonadotropin-releasing hormone (GnRH) analogues. Here's a summary of their possible benefits, side effects and long-term effects.

What do puberty blockers do?

When taken regularly, GnRH analogues stop the body from making sex hormones. That includes testosterone and estrogen.

Sex hormones affect:

• Primary sex characteristics. These are the sexual organs present at birth. They include the penis, scrotum and testicles, and the uterus, ovaries and vagina.
• Secondary sex characteristics. These are the physical changes in the body that appear during puberty. Examples include breast development and growth of facial hair.

In people assigned male at birth, GnRH analogues slow the growth of facial and body hair, prevent voice deepening, and limit the growth of the penis, scrotum and testicles.

In people assigned female at birth, this treatment limits or stops breast development and stops menstruation.

What are the possible benefits of puberty blockers?

Gender identity is the internal sense of being male, female, neither or some combination of both. Gender dysphoria is a feeling of distress that can happen when gender identity differs from a person's sex assigned at birth or from sex-related physical characteristics. Some transgender and gender-diverse people experience gender dysphoria. Others do not.

For transgender and gender-diverse youth who have gender dysphoria, delaying puberty might:

• Improve mental well-being.
• Ease depression and anxiety.
• Improve social interactions with others.
• Lower the need for future surgeries.
• Ease thoughts or actions of self-harm.

Taking puberty blockers alone, however, without other medical or behavioral treatment, might not be enough to ease gender dysphoria.

What are the criteria for use of puberty blockers?

In most cases, to begin using puberty blockers, an individual needs to:

• Show a lasting pattern of gender nonconformity or gender dysphoria.
• Have gender dysphoria that began or worsened at the start of puberty.
• Address any psychological, medical or social problems that could interfere with the treatment.
• Be able to understand the treatment and agree to have it. This is called informed consent.

Puberty blockers are not recommended for children who have not started puberty.

In most cases, youth aren't old enough to get medical treatment without a parent, guardian or other caregiver's permission. This is called medical consent. For those who haven't reached the age of medical consent, a parent, guardian or caregiver often needs to agree to the use of puberty blockers. Parent and family support and encouragement also has been shown to be an important part of boosting mental health and well-being throughout this treatment.

Are the changes permanent?

GnRH analogues don't cause permanent physical changes. Instead, they pause puberty. That offers a chance to explore gender identity. It also gives youth and their families time to plan for the psychological, medical, developmental, social and legal issues that may lie ahead..

When a person stops taking GnRH analogues, puberty starts again.

When does treatment usually start and end?

In general, puberty begins around age 10 or 11, though it may start earlier or later. The effect of puberty blockers depends on when a person begins to take the medicine. GnRH analogue treatment can begin at the start of puberty to delay the development of secondary sex characteristics. In slightly later stages of puberty, the treatment could be used to stop menstruation or erections. It also may prevent further development of secondary sex characteristics.

While many people take the medicine for a few years, everyone is different. After delaying puberty for several years, some teens might decide to stop taking puberty-blocking medicine. Or they may start taking hormones that match their gender identity. This is called gender-affirming hormone therapy.

How is the medication given?

GnRH analogue medicine is prescribed, given and monitored by a health care professional who has expertise in this group of medicines. The medicine typically is given as a shot either monthly, every three months or every six months. Or it may be given as an implant placed under the skin of the upper arm. The implant usually needs to be replaced every 12 months.

While taking puberty blockers, regular blood tests are needed to check the medicine's effectiveness. Regular appointments with the health care team to check for side effects also are important.

What are the possible side effects and complications?

Possible side effects of GnRH analogue treatment include:

• Swelling at the site of the shot.
• Weight gain.
• Hot flashes.
• Mood changes.

Use of GnRH analogues also might have long-term effects on:

• Growth spurts.
• Bone growth.
• Bone density.
• Fertility, depending on when the medicine is started.

If individuals assigned male at birth begin using GnRH analogues early in puberty, they might not develop enough skin on the penis and scrotum to be able to have some types of gender-affirming surgeries later in life. But other surgery approaches usually are available.

Those who take GnRH analogues typically have their height checked every few months. Yearly bone density and bone age tests may be advised. To support bone health, youth taking puberty blockers may need to take calcium and vitamin D supplements.

It's important to stay on schedule with all medical appointments. Between appointments, contact a member of the health care team if any changes cause concern.

What other treatments are needed?

Assessment and counseling by a behavioral health care professional can help youth and their families as they move through the decision-making process about puberty blockers. Behavioral health care also is an important source of support while taking puberty blockers. Talking about an individual's gender identity with teachers, school staff, and staff in other organizations in which the youth is involved also may help ease social adjustment during this time.

After a time of adjusting to puberty blockers and confirming gender identity, gender-affirming hormone therapy might be an option. This can develop masculine or feminine secondary sex characteristics to help better align the body with an individual's gender identity. Some of the changes triggered by gender-affirming hormone therapy cannot be reversed. Others may require surgery to reverse.

GnRH analogues are the most common medicines used to delay puberty. But they are not the only medicines that can be used. Talk to a member of the health care team for information about other treatment choices.

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• AskMayoExpert. Gender diversity in childhood and adolescence. Mayo Clinic; 2023.
• Coleman E, et al. Standards of Care for the Health of Transsexual, Transgender and Gender Nonconforming People. 8th version. World Professional Association for Transgender Health; 2022. https://www.wpath.org/publications/soc. Accessed March 22, 2023.
• Olson-Kennedy J, et al. Management of transgender and gender-diverse children and adolescents. https://www.uptodate.com/contents/search. Accessed March 23, 2023.
• Health Education & Content Services. Puberty blockers for transgender and gender non-conforming youth. Mayo Clinic; 2022.

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Trans kids’ treatment can start younger, new guidelines say

This photo provided by Laura Short shows Eli Bundy on April 15, 2022 at Deception Pass in Washington. In South Carolina, where a proposed law would ban transgender treatments for kids under age 18, Eli Bundy hopes to get breast removal surgery next year before college. Bundy, 18, who identifies as nonbinary, supports updated guidance from an international transgender health group that recommends lower ages for some treatments. (Laura Short via AP)

FILE - Dr. David Klein, right, an Air Force Major and chief of adolescent medicine at Fort Belvoir Community Hospital, listens as Amanda Brewer, left, speaks with her daughter, Jenn Brewer, 13, as the teenager has blood drawn during a monthly appointment for monitoring her treatment at the hospital in Fort Belvoir, Va., on Sept. 7, 2016. Brewer is transitioning from male to female. (AP Photo/Jacquelyn Martin, File)

• Copy Link copied

A leading transgender health association has lowered its recommended minimum age for starting gender transition treatment, including sex hormones and surgeries.

The World Professional Association for Transgender Health said hormones could be started at age 14, two years earlier than the group’s previous advice, and some surgeries done at age 15 or 17, a year or so earlier than previous guidance. The group acknowledged potential risks but said it is unethical and harmful to withhold early treatment.

The association provided The Associated Press with an advance copy of its update ahead of publication in a medical journal, expected later this year. The international group promotes evidence-based standards of care and includes more than 3,000 doctors, social scientists and others involved in transgender health issues.

The update is based on expert opinion and a review of scientific evidence on the benefits and harms of transgender medical treatment in teens whose gender identity doesn’t match the sex they were assigned at birth, the group said. Such evidence is limited but has grown in the last decade, the group said, with studies suggesting the treatments can improve psychological well-being and reduce suicidal behavior.

Starting treatment earlier allows transgender teens to experience physical puberty changes around the same time as other teens, said Dr. Eli Coleman, chair of the group’s standards of care and director of the University of Minnesota Medical School’s human sexuality program.

But he stressed that age is just one factor to be weighed. Emotional maturity, parents’ consent, longstanding gender discomfort and a careful psychological evaluation are among the others.

“Certainly there are adolescents that do not have the emotional or cognitive maturity to make an informed decision,” he said. “That is why we recommend a careful multidisciplinary assessment.”

The updated guidelines include recommendations for treatment in adults, but the teen guidance is bound to get more attention. It comes amid a surge in kids referred to clinics offering transgender medical treatment , along with new efforts to prevent or restrict the treatment.

Many experts say more kids are seeking such treatment because gender-questioning children are more aware of their medical options and facing less stigma.

Critics, including some from within the transgender treatment community, say some clinics are too quick to offer irreversible treatment to kids who would otherwise outgrow their gender-questioning.

Psychologist Erica Anderson resigned her post as a board member of the World Professional Association for Transgender Health last year after voicing concerns about “sloppy” treatment given to kids without adequate counseling.

She is still a group member and supports the updated guidelines, which emphasize comprehensive assessments before treatment. But she says dozens of families have told her that doesn’t always happen.

“They tell me horror stories. They tell me, ‘Our child had 20 minutes with the doctor’” before being offered hormones, she said. “The parents leave with their hair on fire.’’

Estimates on the number of transgender youth and adults worldwide vary, partly because of different definitions. The association’s new guidelines say data from mostly Western countries suggest a range of between a fraction of a percent in adults to up to 8% in kids.

Anderson said she’s heard recent estimates suggesting the rate in kids is as high as 1 in 5 — which she strongly disputes. That number likely reflects gender-questioning kids who aren’t good candidates for lifelong medical treatment or permanent physical changes, she said.

Still, Anderson said she condemns politicians who want to punish parents for allowing their kids to receive transgender treatment and those who say treatment should be banned for those under age 18.

“That’s just absolutely cruel,’’ she said.

Dr. Marci Bowers, the transgender health group’s president-elect, also has raised concerns about hasty treatment, but she acknowledged the frustration of people who have been “forced to jump through arbitrary hoops and barriers to treatment by gatekeepers ... and subjected to scrutiny that is not applied to another medical diagnosis.’’

Gabe Poulos, 22, had breast removal surgery at age 16 and has been on sex hormones for seven years. The Asheville, North Carolina, resident struggled miserably with gender discomfort before his treatment.

Poulos said he’s glad he was able to get treatment at a young age.

“Transitioning under the roof with your parents so they can go through it with you, that’s really beneficial,’’ he said. “I’m so much happier now.’’

In South Carolina, where a proposed law would ban transgender treatments for kids under age 18, Eli Bundy has been waiting to get breast removal surgery since age 15. Now 18, Bundy just graduated from high school and is planning to have surgery before college.

Bundy, who identifies as nonbinary, supports easing limits on transgender medical care for kids.

“Those decisions are best made by patients and patient families and medical professionals,’’ they said. “It definitely makes sense for there to be fewer restrictions, because then kids and physicians can figure it out together.’’

Dr. Julia Mason, an Oregon pediatrician who has raised concerns about the increasing numbers of youngsters who are getting transgender treatment, said too many in the field are jumping the gun. She argues there isn’t strong evidence in favor of transgender medical treatment for kids.

“In medicine ... the treatment has to be proven safe and effective before we can start recommending it,’’ Mason said.

Experts say the most rigorous research — studies comparing treated kids with outcomes in untreated kids — would be unethical and psychologically harmful to the untreated group.

The new guidelines include starting medication called puberty blockers in the early stages of puberty, which for girls is around ages 8 to 13 and typically two years later for boys. That’s no change from the group’s previous guidance. The drugs delay puberty and give kids time to decide about additional treatment; their effects end when the medication is stopped.

The blockers can weaken bones, and starting them too young in children assigned males at birth might impair sexual function in adulthood, although long-term evidence is lacking.

The update also recommends:

—Sex hormones — estrogen or testosterone — starting at age 14. This is often lifelong treatment. Long-term risks may include infertility and weight gain, along with strokes in trans women and high blood pressure in trans men, the guidelines say.

—Breast removal for trans boys at age 15. Previous guidance suggested this could be done at least a year after hormones, around age 17, although a specific minimum ag wasn’t listed.

—Most genital surgeries starting at age 17, including womb and testicle removal, a year earlier than previous guidance.

The Endocrine Society, another group that offers guidance on transgender treatment, generally recommends starting a year or two later, although it recently moved to start updating its own guidelines. The American Academy of Pediatrics and the American Medical Association support allowing kids to seek transgender medical treatment, but they don’t offer age-specific guidance.

Dr. Joel Frader, a Northwestern University a pediatrician and medical ethicist who advises a gender treatment program at Chicago’s Lurie Children’s Hospital, said guidelines should rely on psychological readiness, not age.

Frader said brain science shows that kids are able to make logical decisions by around age 14, but they’re prone to risk-taking and they take into account long-term consequences of their actions only when they’re much older.

Coleen Williams, a psychologist at Boston Children’s Hospital’s Gender Multispecialty Service, said treatment decisions there are collaborative and individualized.

“Medical intervention in any realm is not a one-size-fits-all option,” Williams said.

Follow AP Medical Writer Lindsey Tanner at @LindseyTanner.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

Hormonal Gender Reassignment Treatment for Gender Dysphoria

Affiliation.

• 1 Medical Clinic I: Gastroenterology and Hepatology, Pneumology and Allergology, Endocrinology and Diabetology, Nutritional Medicine, University Hospital Frankfurt, Frankfurt, Germany.
• PMID: 33559593
• PMCID: PMC7871443
• DOI: 10.3238/arztebl.2020.0725

Background: No data are available at present on the prevalence of gender dysphoria (trans-identity) in Germany. On the basis of estimates from the Netherlands, it can be calculated that approximately 15 000 to 25 000 persons in Germany are affected. Persons suffering from gender dysphoria often experience significant distress and have a strong desire for gender reassignment treatment.

Methods: This review is based on pertinent publications retrieved by a selective search in the PubMed database employing the searching terms "transsexualism," "transgender," "gender incongruence," "gender identity disorder," "gender-affirming hormone therapy," and "gender dysphoria."

Results: In view of its far-reaching consequences, some of which are irreversible, hormonal gender reassignment treatment should only be initiated after meticulous individual consideration, with the approval of the treating psychiatrist/psychotherapist and after extensive information of the patient by an experienced endo - crinologist. Before the treatment is begun, the patient must be extensively screened for risk factors. The contraindications include severe preexisting thromboembolic diseases (mainly if untreated), hormone-sensitive tumors, and uncontrolled pre - existing chronic diseases such as arterial hypertension and epilepsy. Finding an appropriate individual solution is the main objective even if contraindications are present. Male-to-female treatment is carried out with 17β-estradiol or 17β-estradiol valerate in combination with cyproterone acetate or spironolactone as an antiandrogen, female-to-male treatment with transdermal or intramuscular testosterone preparations. The treatment must be monitored permanently with clinical and laboratory follow-up as well as with gynecological and urological early-detection screening studies. Prospective studies and a meta-analysis (based on low-level evidence) have documented an improvement in the quality of life after gender reassignment treatment. Female-to-male gender-incongruent persons often have difficulty being accepted in a gynecological practice as a male patient.

Concluzion: Further prospective studies for the quantification of the risks and benefits of hormonal treatment would be desirable. Potential interactions of the hormone preparations with other medications must always be considered.

Publication types

• Meta-Analysis
• Gender Dysphoria* / drug therapy
• Germany / epidemiology
• Prospective Studies
• Quality of Life
• Sex Reassignment Surgery*
• Transgender Persons*
• Transsexualism*

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• Long term hormonal...

Long term hormonal treatment for transgender people

• Related content
• Peer review
• Martin den Heijer , professor of endocrinology 1 2 ,
• Alex Bakker , transgender man with 20 years of experience taking hormonal treatment ,
• Louis Gooren , emeritus professor in transgender medicine 2
• 1 Department of internal medicine, VU Medical Center, Amsterdam, Netherlands
• 2 Center of expertise on gender dysphoria, VU Medical Center, Amsterdam, Netherlands
• Correspondence to M den Heijer m.denheijer{at}vumc.nl

What you need to know

Transgender people using hormone treatment need lifelong medical support and care. Hormonal treatment for gender dysphoria resembles hormone replacement therapy for people with hypogonadism.

Hormone treatment in transgender people is accepted to be safe and increases overall wellbeing in most people. The most common (though rare) side effects are venous thrombosis in trans women due to oestrogens and polycythaemia caused by androgens in trans men.

Some trans women will not have had their prostate removed and some trans men keep their ovaries. Be aware of the risk of cancer in these sites and think about the added risk of hormone supplementation.

The aim of hormone treatment in transgender people is to adjust their secondary sex characteristics to be more congruent with their experienced gender. Hormone treatment for transgender people is usually initiated by specialist gender clinics, but some people start hormone treatment of their own accord without a prescription. With growing numbers of transgender people presenting to healthcare services (estimated as 9.2 per 100 000 1 ), general practitioners, general endocrinologists, and other doctors will become increasingly involved in their long term care, the prescription of hormones, and consideration of potential side effects. Several guidelines are available on the start of hormonal treatment 2 3 4 5 6 7 ; the focus of this article is the long term hormonal care for transgender people who might no longer attend a specialist clinic. It is aimed at a more general readership of physicians occasionally seeing adult transgender people.

Transgender terminology

Language and terminology are sensitive. Some terms used in the past are no longer appropriate because they might have negative connotations.

The term gender has historically been used to refer to psychological, behavioural, and sociological characteristics, and their categorisation by society as “masculine” or “feminine.” The term sex has historically been used to refer to biological characteristics similarly categorised. Transgender people stress the importance of proper language that respects their identity. Terms like male-to-female transgender or cross-sex hormonal therapy might therefore not be appropriate because they suppose a binary view. Even the distinction between gender and sex might be perceived as an oversimplification. Be sensitive to a person’s own use of terminology and interpretation of their identity. If in doubt, ask your patient what language they prefer.

Trans woman

A woman who was assigned male at birth.

A man who was assigned female at birth.

In this article we use these terms also for people who identify as non-binary transgender and wish for partial changes. Attending physicians should be aware of possible medical problems resulting from biological aspects of the sex at birth. For example, prostate cancer in a trans woman.

Non-binary/Gender-queer

The terms “non-binary” and “gender-queer” are used by people who do not exclusively identify as man or woman, masculine or feminine, male or female.

Anti-androgens

Agents antagonising testosterone action.

Anti-gonadotropics

Agents that inhibit secretion of luteinising and follicle stimulating hormones from the pituitary.

Hormone treatment in transgender people

Many transgender people seek to adjust their physique to be more congruent with their experienced gender by using hormone treatments and/or undergoing surgical interventions. The broad aims of hormone treatment in adult transgender people are to eliminate as far as desired the earlier hormonal effects of the sex steroids of their sex at birth and to induce the desired secondary sex characteristics of the experienced gender.

Hormone preparations that are used in transgender medicine for gender dysphoria are the same that are used in gonadal endocrinology, although they are usually not licensed for treating gender dysphoria in itself. Table 1 lists these preparations.

Hormones used in transgender persons with typical doses in adults (20-50 years)

• View inline

Hormones induce more than one effect. Oestrogens, for example, influence breast growth, bone density, skin, and the clotting system. Generally, it is not possible to selectively stimulate one effect and inhibit another. The effects of gonadal hormones can differ between persons because of the individual properties of the hormone receptors. Some people show a clear change in fat distribution pattern but little breast development, while in others the opposite occurs. In general, regular hormone treatment is needed for two to three years to reach its effect. 3

Hormone treatment for trans women

The key element in treating trans women is the administration of oestrogens. Guidelines recommend using the natural form 17 β-oestradiol because ethinyloestrogen (common in oral contraceptives) has been associated with a strong increase in the risk of venous thrombosis and cardiovascular disease. 8 Progestogens cause no additional feminisation effect when prescribed alongside oestrogens.

Anti-androgen

In some people, oestrogen administration only suppresses testosterone below the upper level of cis (ie, persons for whom their gender identity matches their sex at birth). To achieve full suppression in all people, most guidelines recommend the use of oestrogen in combination with a testosterone suppressing agent. 3 7 Testosterone suppressing agents (or anti-androgens) of several pharmacological classes are available ( table 1 ). GnRH agonists are effective but more expensive (€100-150 per month). They are first line treatment in the UK. Cyproterone acetate combines anti-androgenic and anti-gonadotropic effects and is widely used in continental Europe. Spironolactone is an aldosterone antagonist with anti-androgenic properties and is used as anti-androgen primarily in the US. A recent study showed comparable effect of GnRH analogues instead of cyproterone acetate in suppressing testosterone levels. 9 If trans women have undergone orchidectomy (as part of the surgical reassignment), anti-testosterone treatment could be stopped.

Clinical effect

Important effects of combined oestrogen and anti-testosterone treatment include breast development, softer skin, loss of sexual hair growth, increase in fat mass, broader hips, a decrease of lean body mass, and a decrease or change in libido with clinically relevant mood changes. 7 Not all effects are as strong in every person. Sometimes, additional measures are needed to achieve the desired effects, such as laser and electrolysis to remove unwanted hair, or breast augmentation to achieve sufficient breast volume.

Hormone treatment for trans men

Testosterone.

In trans men, testosterone is the key hormone administered and no anti-oestrogens are needed. 6 Testosterone is converted to oestradiol (by aromatase activity in fat cells) in men and women and oestradiol plays an important role in bone physiology in cis men and trans men. 10

Important effects of testosterone are an increase in lean body mass and muscle strength, body and hair growth in a male pattern, and lowering of the voice. Testosterone supplementation given in the doses in table 1 leads to cessation of monthly periods. If uterine bleeding persists, a GnRH agonist or progestin (lynestrenol 5 mg daily or medroxyprogesterone 10 mg three times daily or another progestin) could be added to stop uterine bleeding.

Principles of dosing

Most guidelines state that dosing of hormones should be guided by blood levels of oestradiol and testosterone, based on mean levels of the desired gender. These levels are often achieved with the dosages mentioned above; however, hormone levels are not a goal in themselves. The primary goals are usually a degree of feminisation or masculinisation as specified by the patient, which are achieved with their fullest effects after two to five years, similar to the temporal pattern of hormonal puberty. After this period, the goal for hormonal treatment—especially if in the meantime the gonads have been removed—might be to avoid signs and symptoms of hypogonadism such as mood changes, fatigue, osteoporosis, and muscle weakness. While dosage advice and target levels are an aid to avoiding underdosing and overdosing, one should be aware that, due to hormone receptor properties, similar levels can have different biological effects in different individuals, and different individuals can have different ideas about the desired outcome. In other words: the clinical effects and wellbeing of the trans person are paramount, not the hormone levels themselves. This applies also to persons who do not fit in the male/female distinction (non-binary or gender queer). It is possible to achieve hormone levels that are in between male and female reference ranges for both testosterone and oestradiol, but it is important to avoid hypogonadism in patients that already have gonadectomy in order to prevent bone loss and other consequences of hypogonadism.

How well does it work and how safe is it?

It has been shown that hormone treatment in transgender people with gender dysphoria increases wellbeing in most people. 11 12 13 From a medical point of view, hormonal treatment seems to be acceptably safe. 14 15

Oestrogens increases the risk of venous thrombosis, but a study in trans women showed that long term treatment with oestrogen yields only a low thrombotic risk (one event in 1,286 person years). 16 Oral oestradiol supplementation has a more prothrombotic effect than parenteral oestradiol supplementation; therefore it might be recommended to use parenteral supplementation in people with a higher risk for venous thrombosis (ie, family history of thrombosis or age over 50). 17

Testosterone-blockers can have their own side effects, such as hyperprolactinaemia 18 and an increased risk for meningioma with cyproterone acetate (although still very rare), 19 and high potassium levels with spironolactone.

Testosterone supplementation increases the haematocrit into the male reference range and can sometimes lead to polycythaemia 20 ; therefore monitoring haematocrit is recommended every three months in the first year and them one to two times per year. 3 Liver toxicity of testosterone has been described but is rare, and no liver function tests are recommended. 3

Bone and cardiovascular disease

Bone density can be affected, but both testosterone and oestrogen in recommended dosages lead to an increase in bone density. 21 22 In general, oestradiol for trans women has a beneficial effect on cardiovascular risk factors, while testosterone for trans men has a detrimental effect. 23 But limited experience points in the opposite direction for cardiovascular disease itself: an increase in cardiovascular disease in oestrogen users (particularly ethinyl oestradiol) and decrease in testosterone users. 24 No clear explanations for this paradoxical finding are available yet.

Malignancies

Cases of cancer of the prostate and breast have been reported but recent studies showed no increased overall risk, although the estimated breast cancer risk in trans women is 33 times higher compared with cis men. 25 26 27 28

However, much of what we know about the effects of hormone treatment in transgender people is from relatively small studies ( table 2 ). Large, well designed studies, particularly in ageing subjects, are urgently needed to collect reliable estimates on effects and side effects.

Possible areas of concern in the long term follow-up of transgender persons on hormonal treatment and practical recommendations

Long term follow-up

Hormone supplementation is in principle lifelong, and people benefit from regular (yearly or two yearly) supervision by a doctor with an understanding of transgender health and hormone prescription.

Follow-up might take place in a specialist gender clinic, or with a primary care physician or other generalist with sufficient training in hormonal supplementation. Long term follow-up would include checking the hormone levels in trans men and trans women and haematocrit in trans men at every visit (yearly or two yearly). Other measurements must be guided by risk factors of the individual, such as blood lipids in case of cardiovascular risk. If there are sex specific laboratory reference values, use the reference values of the person’s new gender. 30 An exception is bone density measurement. From puberty on there are sex specific increases in bone mineral density, and reference values of the sex at birth should be used for assessment of T and Z values.

Trans women can develop prostate cancer, and breast cancer can develop in minimal residual breast cells in trans men. It would be important to consider and discuss withdrawal of hormonal treatment in these situations. We advise following the local guidelines for population screening of the cis population according to the relevant anatomy present (either prostate, cervix, or breasts).

Transgender elderly

Sex hormones rise in puberty. There is a sharp drop at menopause in women and a more gradual decrease in men. Data are lacking on whether to follow these patterns in transgender people. Many transgender people prefer to continue hormone use. The side effects of prolonged supplementation at dosages that induce young adult levels are not well studied. In our view, it seems prudent to taper the dose at increasing age, but there are no clinical data to support or dissuade from this approach. It is important, therefore, to discuss this uncertainty with the person and frame it in a general discussion about their overall health. 31

Education into practice

How confident do you feel about discussing hormone treatment with trans people in your practice?

Are you aware of any resources that might support you with their longer term care?

What might you do differently as a result of reading this article?

How patients were involved in the creation of this article

Our author group includes a trans person. The review group included a trans person. AB was asked to join us as author to enhance the patient perspective. AB is trans man with 20 years of experience taking hormonal therapy. Our first version was extensively reviewed by five reviewers (including a trans person). Their comments helped us to improve the manuscript, especially in the use of sensitive phrasing.

How this article was made

A first draft was written by MdH and LG with focus on long term hormonal treatment. We performed a search in www.pubmed.gov with search term “transgender OR transsexual” and “hormones OR oestrogen OR testosterone,” which revealed 485 papers. We largely focused on papers that were published in English in the last five years. AB was asked to join us as author to enhance the patient perspective. Our first version was extensively reviewed by five reviewers (including a trans person) and the BMJ editor. Their comments were very helpful in improving and clarifying the manuscript. They helped us to broaden the scope to practices used in other countries as well.

Case Vignettes

A 66 year old trans woman comes to her general practitioner. She started oral oestradiol (4 mg daily) 10 years ago together with an anti-androgen (cyproterone acetate 50 mg daily). She decided not to have a vaginoplasty because of the risk of complications of her obesity (she has a body mass index of 40). Two weeks ago, she was diagnosed with a deep vein thrombosis of the left leg and she commenced warfarin. She now wonders if she should stop her hormone treatment.

To consider

It is widely believed that there is a relationship between oestrogens and venous thrombosis. However, most evidence is based on cis women that use ethinyl oestradiol in combination with a prostagen. Little is known about the thrombogenicity of cyproterone acetate, although the combination of ethinyl oestradiol and cyproterone acetate in cis women is associated with increased thrombosis risk. 32 In this trans woman we would advise that she switches the cyproterone acetate for a GnRH analogue. If she wants to continue the oestrogens we would advise that she switches to a transdermal method of application.

A 36 year old trans man comes for his biannual visit to his endocrinologist. He started testosterone injections (250 mg every two weeks) eight years ago. He is feeling well, works as a bus driver, and smokes 20 cigarettes a day. His blood tests show testosterone of 15 nmol/L just before the next injections. Haematocrit is 0.55.

The definition of polycythaemia in terms of haematocrit levels differs among guidelines, but 0.55 is high. Our first advice would be to quit smoking. Furthermore, a short-acting (2-3 week) course of testosterone injections gives high peak levels and is associated with higher haematocrit levels. Therefore, we would advise he switch to either a testosterone gel or a long acting testosterone injection.

This is one of a series of occasional articles on therapeutics for common or serious conditions, covering new drugs and old drugs with important new indications or concerns. The series advisers are Robin Ferner, honorary professor of clinical pharmacology, University of Birmingham and Birmingham City Hospital, and Albert Ferro, professor of cardiovascular clinical pharmacology, King’s College London. To suggest a topic, please email us at [email protected].

We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: none.

Provenance and peer review: Commissioned; externally peer reviewed.

Patient consent not applicable.

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Treatment - Gender dysphoria

Treatment for gender dysphoria aims to help people live the way they want to, in their preferred gender identity or as non-binary.

What this means will vary from person to person, and is different for children, young people and adults. Waiting times for referral and treatment are currently long.

Treatment for children and young people

If your child may have gender dysphoria, they'll usually be referred to one of the NHS Children and Young People's Gender Services .

Your child or teenager will be seen by a multidisciplinary team including a:

• clinical psychologist
• child psychotherapist
• child and adolescent psychiatrist
• family therapist
• social worker

The team will carry out a detailed assessment, usually over 3 to 6 appointments over a period of several months.

Depending on the results of the assessment, options for children and teenagers include:

• family therapy
• individual child psychotherapy
• parental support or counselling
• group work for young people and their parents
• regular reviews to monitor gender identity development
• referral to a local Children and Young People's Mental Health Service (CYPMHS) for more serious emotional issues

Most treatments offered at this stage are psychological rather than medical. This is because in many cases gender variant behaviour or feelings disappear as children reach puberty.

Hormone therapy in children and young people

Some young people with lasting signs of gender dysphoria who meet strict criteria may be referred to a hormone specialist (consultant endocrinologist). This is in addition to psychological support.

Puberty blockers and gender-affirming hormones

Puberty blockers (gonadotrophin-releasing hormone analogues) are not available to children and young people for gender incongruence or gender dysphoria because there is not enough evidence of safety and clinical effectiveness.

From around the age of 16, young people with a diagnosis of gender incongruence or gender dysphoria who meet various clinical criteria may be given gender-affirming hormones alongside psychosocial and psychological support.

These hormones cause some irreversible changes, such as:

• breast development (caused by taking oestrogen)
• breaking or deepening of the voice (caused by taking testosterone)

Long-term gender-affirming hormone treatment may cause temporary or even permanent infertility.

However, as gender-affirming hormones affect people differently, they should not be considered a reliable form of contraception.

There is some uncertainty about the risks of long-term gender-affirming hormone treatment.

Children, young people and their families are strongly discouraged from getting puberty blockers or gender-affirming hormones from unregulated sources or online providers that are not regulated by UK regulatory bodies.

Transition to adult gender identity services

Young people aged 17 or older may be seen in an adult gender identity clinic or be referred to one from a children and young people's gender service.

By this age, a teenager and the clinic team may be more confident about confirming a diagnosis of gender dysphoria. If desired, steps can be taken to more permanent treatments that fit with the chosen gender identity or as non-binary.

Treatment for adults

Adults who think they may have gender dysphoria should be referred to a gender dysphoria clinic (GDC).

Find an NHS gender dysphoria clinic in England .

GDCs have a multidisciplinary team of healthcare professionals, who offer ongoing assessments, treatments, support and advice, including:

• psychological support, such as counselling
• cross-sex hormone therapy
• speech and language therapy (voice therapy) to help you sound more typical of your gender identity

For some people, support and advice from the clinic are all they need to feel comfortable with their gender identity. Others will need more extensive treatment.

Hormone therapy for adults

The aim of hormone therapy is to make you more comfortable with yourself, both in terms of physical appearance and how you feel. The hormones usually need to be taken for the rest of your life, even if you have gender surgery.

It's important to remember that hormone therapy is only one of the treatments for gender dysphoria. Others include voice therapy and psychological support. The decision to have hormone therapy will be taken after a discussion between you and your clinic team.

In general, people wanting masculinisation usually take testosterone and people after feminisation usually take oestrogen.

Both usually have the additional effect of suppressing the release of "unwanted" hormones from the testes or ovaries.

Whatever hormone therapy is used, it can take several months for hormone therapy to be effective, which can be frustrating.

It's also important to remember what it cannot change, such as your height or how wide or narrow your shoulders are.

The effectiveness of hormone therapy is also limited by factors unique to the individual (such as genetic factors) that cannot be overcome simply by adjusting the dose.

Find out how to save money on prescriptions for hormone therapy medicines with a prescription prepayment certificate .

Risks of hormone therapy

There is some uncertainty about the risks of long-term cross-sex hormone treatment. The clinic will discuss these with you and the importance of regular monitoring blood tests with your GP.

The most common risks or side effects include:

• blood clots
• weight gain
• dyslipidaemia (abnormal levels of fat in the blood)
• elevated liver enzymes
• polycythaemia (high concentration of red blood cells)
• hair loss or balding (androgenic alopecia)

There are other risks if you're taking hormones bought over the internet or from unregulated sources. It's strongly recommended you avoid these.

Long-term cross-sex hormone treatment may also lead, eventually, to infertility, even if treatment is stopped.

The GP can help you with advice about gamete storage. This is the harvesting and storing of eggs or sperm for your future use.

Gamete storage is sometimes available on the NHS. It cannot be provided by the gender dysphoria clinic.

Read more about fertility preservation on the HFEA website.

Surgery for adults

Some people may decide to have surgery to permanently alter body parts associated with their biological sex.

Based on the recommendations of doctors at the gender dysphoria clinic, you will be referred to a surgeon outside the clinic who is an expert in this type of surgery.

In addition to you having socially transitioned to your preferred gender identity for at least a year before a referral is made for gender surgery, it is also advisable to:

• lose weight if you are overweight (BMI of 25 or over)
• have taken cross-sex hormones for some surgical procedures

It's also important that any long-term conditions, such as diabetes or high blood pressure, are well controlled.

Surgery for trans men

Common chest procedures for trans men (trans-masculine people) include:

• removal of both breasts (bilateral mastectomy) and associated chest reconstruction
• nipple repositioning
• dermal implant and tattoo

Gender surgery for trans men includes:

• construction of a penis (phalloplasty or metoidioplasty)
• construction of a scrotum (scrotoplasty) and testicular implants
• a penile implant

Removal of the womb (hysterectomy) and the ovaries and fallopian tubes (salpingo-oophorectomy) may also be considered.

Surgery for trans women

Gender surgery for trans women includes:

• removal of the testes (orchidectomy)
• removal of the penis (penectomy)
• construction of a vagina (vaginoplasty)
• construction of a vulva (vulvoplasty)
• construction of a clitoris (clitoroplasty)

Breast implants for trans women (trans-feminine people) are not routinely available on the NHS.

Facial feminisation surgery and hair transplants are not routinely available on the NHS.

As with all surgical procedures there can be complications. Your surgeon should discuss the risks and limitations of surgery with you before you consent to the procedure.

Life after transition

Whether you've had hormone therapy alone or combined with surgery, the aim is that you no longer have gender dysphoria and feel at ease with your identity.

Your health needs are the same as anyone else's with a few exceptions:

• you'll need lifelong monitoring of your hormone levels by your GP
• you'll still need contraception if you are sexually active and have not yet had any gender surgery
• you'll need to let your optician and dentist know if you're on hormone therapy as this may affect your treatment
• you may not be called for screening tests as you've changed your name on medical records – ask your GP to notify you for cervical and breast screening if you're a trans man with a cervix or breast tissue
• trans-feminine people with breast tissue (and registered with a GP as female) are routinely invited for breast screening from the ages of 50 up to 71

Find out more about screening for trans and non-binary people on GOV.UK.

NHS guidelines for gender dysphoria

NHS England has published what are known as service specifications that describe how clinical and medical care is offered to people with gender dysphoria:

• Non-surgical interventions for adults
• Surgical interventions for adults
• Interim service specification for specialist gender incongruence services for children and young people

Review of gender identity services

NHS England has commissioned an independent review of gender identity services for children and young people. The review will advise on any changes needed to the service specifications for children and young people.

Page last reviewed: 28 May 2020 Next review due: 28 May 2023

Gender therapy review reveals devastating impacts on teens

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A top Human Rights Council-appointed expert has welcomed the decision by all health authorities in the United Kingdom to halt the routine use of puberty-blockers offered to children as part of gender transition services, amid a sharp increase more widely in the number of teenage girls seeking such treatment and concerns that it might disrupt brain development.

The development is in line with several western European countries that have reportedly reduced access to similar gender identity treatments whose benefits were found to be “remarkably weak”, according to a National Health Service (NHS) England-commissioned review, published on 10 April by consultant paediatrician Dr. Hilary Cass.

UN Special Rapporteur Reem Alsalem also welcomed the commitment by the UK Secretary of State for Health and Social Care to implement the implications of the Cass Review.

It “has…very clearly shown the devastating consequences that policies on gender treatments have had on human rights of children , including girls… its implications go beyond the UK,” said the UN Special Rapporteur on violence against women and girls, Ms. Alsalem.

UN_SPExperts

Referrals spike

The independent rights expert cited the Review’s findings that between 2009 and 2016, the number of adolescent girls referred to NHS-England’s service for gender distress – or dysphoria - increased from just 15 to 1,071.

These referrals “breached fundamental principles, such as the need to uphold the best interest of the child in all decisions that affect their lives ”, the Special Rapporteur insisted, while transgender rights groups have maintained that there are long waiting lists for treatment.

Mental anguish

Noting the “extraordinarily high number of teenage girls” impacted by anxiety and depression in recent years, Ms. Alsalem said it was crucially important that health authorities stopped “rapidly initiating permanent gender transition pathways that usually begin with puberty blockers, which could cause temporary or permanent disruption to brain maturation ”.

Instead, girls potentially seeking “gender affirming interventions” should be offered more holistic psychological support, protected by legislation that should ensure “transition does not become the only option that is acceptable to discuss with them”.

‘Detransition’ support

The same opportunity for wider therapeutic support should also be available to “detransitioners” - individuals who have discontinued gender transitioning - “most of whom are girls”, Ms. Alsalem maintained, in support of the Review’s findings.

“ Far too long, the suffering of this group of children and adults has been ignored or discounted. The report’s findings and recommendation signals that they have been heard, seen, and that their specific needs have been recognised.”

Toxic debate

According to Dr Cass’s report, “many more” young girls are being referred for gender transition treatment today, marking a distinct change from the past, when most requests for medical help came from adolescent boys.

Reiterating an earlier call for tolerance regarding discussions surrounding gender treatments amid a “toxicity of the debate” identified by the Cass Review, Special Rapporteur Alsalem stressed that researchers and academics who expressed their views should not be “silenced, threatened or intimidated” .

Special Rapporteurs are not UN staff and are independent from any government or organization. They serve in their individual capacity and receive no salary for their work.

• women and girls

Medications for Gender Affirming Hormone Therapy

Other names: GAHT

Gender-affirming hormone therapy (GAHT) is used to change secondary sex characteristics to align with gender identity, this can be feminizing or masculinizing hormone therapy.  Hormone therapies are prescription medications that are taken by mouth, patch, gel, or injection.

Drugs used for Gender Affirming Hormone Therapy

The medications listed below are related to or used in the treatment of this condition.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

As Europe pumps breaks on transgender care for minors, US pushes full steam ahead

by KAYLA GASKINS | The National Desk

WASHINGTON (TND) — There’s a shift underway in Europe to restrict medical gender-affirming care for children and teens.

Scotland is the latest to join England, Finland, Norway, Sweden and Denmark to drastically limit the prescriptions of puberty blockers and cross-sex hormone drugs for minors. The restrictions stem from concerns over the effectiveness, safety and long-term impacts of these often irreversible treatments. These concerns were outlined in a report led by Dr. Hilary Cass for NHS England.

World Professional Association for Transgender Health, the leading entity doctors look to for guidance on trans care, issued a statement responding to the Cass report, calling the data they based their decision on “outdated and untrue.” Dr. Cass recently told the New York Times it’s actually U.S. doctors who are “out of date” on youth gender medicine.

As Europe pumps the breaks, America is still pushing full steam ahead.

The Daily Caller News Foundation dug into pediatric transgender care in the U.S. and obtained 30 hours of training videos from WPATH .

"I think it’s important people understand how influential an organization like WPATH actually is," said Kate Anderson, an investigative reporter with the Daily Caller News Foundation. "WPATH has such an influence all the way down to your local pediatrician's office."

The training videos include acknowledgments about the negative side effects of treatments.

"We talk about puberty blockers as reversible. I’m adding an asterisk to it," said one doctor. "There’s challenges with puberty suppression that we have to acknowledge."

"There were several doctors who spoke about the unknowns around giving kids puberty blockers such as the impact on brain development, the impact on fertility, the impact on loss of bone density," explained Megan Brock, another investigative producer with Daily Caller News Foundation who worked on the project.

WPATH training videos also show doctors downplaying evidence-based data when it comes to transgender care.

"Evidence is one part of this but also there’s an ethical human right component to this," explained another doctor. 'We don’t rely on evidence for every single treatment we do in medicine."

Some doctors seemed to brush off the seriousness of these treatments when discussing the consent of those with mental health struggles. Another doctor compared gender reassignment to getting wisdom teeth pulled.

"I would probably frame it, are they mentally stable to go for a wisdom tooth extraction? An elective surgery," the doctor said.

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What Are the Symptoms of High Blood Pressure in Women?

• Hypertension in Women
• Risk in Transgender Women
• How it Affects the Body
• Home Remedies
• When to Seek Care

Roughly half of all American adults have high blood pressure ( hypertension ). Men are more likely to develop high blood pressure than women, with 50% of adult men living with high blood pressure compared to 44% of women.

Left untreated, high blood pressure can damage the blood vessels, heart, brain, and other organs. Hormonal changes due to conditions such as menopause and pregnancy contribute to high blood pressure risk in women.

This article provides a blood pressure chart and describes how high blood pressure affects women.

Mayur Kakade / Getty Images

A Note on Gender and Sex Terminology

Verywell Health acknowledges that  sex and gender  are related concepts, but they are not the same. To reflect our sources accurately, this article uses terms like “female,” “male,” “woman,” and “man” as the sources use them.

What Are High Blood Pressure Levels in Women?

The threshold to diagnose high blood pressure is not gender-specific, meaning that high blood pressure in women is classified the same as high blood pressure in a person of any other gender.

Generally, normal blood pressure is considered 120/80 millimeters of mercury (mm Hg). Above that, a blood pressure of up to 130/80 is considered elevated. Healthcare providers determine your blood pressure stage based on a specific range, as seen in the blood pressure chart below:

Some blood pressure charts consider specific factors, such as age and race or ethnicity.

Symptoms of High Blood Pressure in Women

For most people, high blood pressure develops with no noticeable symptoms over time. When symptoms do occur, they may be more pronounced in women. However, they're often attributed to other health concerns, such as stress, anxiety, or menopause.

Symptoms of High Blood Pressure in Older Women

Older women with stiff or congested arteries are less likely to experience symptoms of high blood pressure compared to younger women, according to some reports. Young to middle-aged women are more likely to experience symptoms of high blood pressure. Examples of these symptoms include:

• Blurred vision
• Chest pain that appears alongside stress, without radiating to other areas
• Fatigue , lack of energy, and difficulty sleeping
• Hot flashes
• Occasional fluid retention in the ankles, hands, or eyes
• Pain that starts in the chest and radiates to the jaw, shoulders, or left arm
• Palpitations , increased heart rates, or atrial fibrillation
• Severe sweating during the day or at night
• Tight, persistent chest pain at rest
• Your bra feels like it's fitting too tight

Many of these symptoms can also overlap with hormonal changes and fluctuations in sex hormones. Menopause (when menstrual periods have seized for 12 months in a row) and pregnancy all play a significant role in the development of high blood pressure in women—especially during middle age.

High Blood Pressure in Transgender Women

If you have undergone any form of gender reassignment therapy, hormonal therapies can have an impact on various physiological processes, including your blood pressure.

One study revealed that gender-affirming hormone therapy (GAHT) can dramatically increase blood pressure levels. However, the young age at which most individuals seek these treatments can be protective against reaching stages 1 or 2 hypertension.

If you have undergone or are planning to seek GAHT, talk to your healthcare team about your medical history and how hormonal therapies can impact your health.

High Blood Pressure and Pregnancy: Understanding Preeclampsia

Hormone levels can trigger changes in blood pressure, which is why pregnant people are at risk for preeclampsia , a high blood pressure condition that occurs during pregnancy. Changing hormone levels, increased fluid retention in the body, and other physical stressors contribute to preeclampsia.

Gestational hypertension and preeclampsia are two severe variations of this condition that can cause problems for pregnant people and their developing fetuses.

All pregnant people should have their blood pressure checked regularly and be screened for conditions like preeclampsia and eclampsia (a seizure disorder in pregnant people). Your healthcare team will monitor your blood pressure closely and suggest treatments based on your blood pressure level and other underlying conditions.

Some risk factors for developing complications with high blood pressure during pregnancy include:

• Kidney disease
• Autoimmune conditions
• Carrying multiples, such as twins or triplets
• A history of preeclampsia during previous pregnancies

Gestational hypertension is usually diagnosed in pregnant people who have normal blood pressure levels before pregnancy but develop blood pressures of 140/90 mm Hg and up in the second half of pregnancy.

Preeclampsia typically appears during the second half of pregnancy, usually in the third trimester. You may be diagnosed with this condition if you have repeated high blood pressure readings alongside proteins in your urine. Certain proteins in the urine are a sign of multi-organ danger and often signal the need for immediate medical treatment—and, in some cases, early delivery.

However, there are other indicators of preeclampsia that may occur without proteins present, such as abnormal kidney function or headaches.

High blood pressure and preeclampsia during pregnancy can put you and your fetus at risk for immediate complications. It can also increase your risk of developing high blood pressure or other cardiovascular problems later in life.

What Uncontrolled Blood Pressure Does to the Body

Untreated high blood pressure can cause permanent damage to your blood vessels, organs, and other body tissues. The strain of increased force of high blood pressure on your blood vessels and tissues—and the extra work your heart does—can cause significant health issues like:

• Heart attack
• Cardiovascular disease
• Kidney damage
• Heart failure
• Vision loss
• Peripheral artery disease
• Sexual dysfunction

How to Treat High Blood Pressure in Women

Treatment options for high blood pressure are similar regardless of gender and usually include a combination of prescription medications, diet modification, and lifestyle changes.

If your blood pressure gets too high, a healthcare provider will prescribe one or more medications to control it, and it's important that you stick to the prescribed regimen.

The classes of medications most often used to treat high blood pressure include:

• Angiotensin converting enzyme (ACE) inhibitors
• Alpha-2 receptor agonists
• Alpha-blockers
• Angiotensin 2 receptor blockers
• Beta-blockers
• Calcium channel blockers
• Combined alpha- and beta-blockers
• Vasodilators

Outside of these medications, though, nondrug strategies can help manage your blood pressure and should be used alongside any medications.

Home Remedies to Lower Blood Pressure Naturally

In addition to medications and meeting regularly with a healthcare provider, strategies such as the following can help you manage and even lower your blood pressure naturally:

• Getting enough sleep
• Exercising regularly
• Reducing stress through meditation

Long-term stress reduction and adherence to a healthy, well-balanced diet can help you manage your blood pressure. It's also important to know how to check your blood pressure at home and what your readings mean.

How to Prevent High Blood Pressure

Maintaining lifelong healthy habits is the best way to prevent high blood pressure. Making healthy changes as you age can help you avoid severe high blood pressure.

Whether you are trying to prevent high blood pressure or you are working to reduce your blood pressure alongside medications, the following measures can help:

• Eating a healthful diet
• Limiting alcohol consumption
• Quitting smoking
• Reducing stress

When to Contact a Healthcare Provider

If your blood pressure readings are high on two or more healthcare visits, your healthcare team will probably start discussing lifestyle changes to prevent high blood pressure and related complications. Depending on your blood pressure stage, a healthcare provider may prescribe medication.

If you have repeated elevated (high) blood pressure readings at home, schedule an appointment to see a healthcare provider.

A blood pressure reading of 180/120 or higher—even on a single occasion—can be a sign of trouble, especially if it appears alongside symptoms like chest pain, vision changes, or headache. If you have a blood pressure reading or symptoms that fall into this category, visit your nearest urgent care or emergency department, or call 911 for immediate medical attention.

Women are less likely than men overall to develop high blood pressure, but the numbers are close, and women may experience symptoms that men don't have. Women are also at risk for high blood pressure when hormone levels change, like during pregnancy or menopause. See a healthcare provider for regular health screenings and blood pressure monitoring.

Centers for Disease Control and Prevention. Facts about hypertension . July 6, 2023.

Reckelhoff JF. Mechanisms of sex and gender differences in hypertension . J Hum Hypertens. 2023;37(596–601). doi:10.1038/s41371-023-00810-4

American Heart Association. High blood pressure.

Centers for Disease Control and Prevention. High blood pressure symptoms and causes . May 18, 2021.

European Society of Cardiology. High blood pressure is the most deadly risk factor for women worldwide . May 17, 2023.

Maas, AH. Hypertension in women: no 'silent' lady-killer . E-Journal of Cardiology Practice . 2019;17(21).

Connelly PJ, Currie G, Delles C. Sex differences in the prevalence, outcomes and management of hypertension .  Curr Hypertens Re. 2022;24:185-192. doi:10.1007/s11906-022-01183-8

Satoh M. Blood pressure changes with gender-affirming hormone therapy in transgender people.   Hypertens Res. 2023;46(792-793). doi:10.1038/s41440-022-01162-1

The American College of Obstetricians and Gynecologists. Preeclampsia and high blood pressure during pregnancy . April 2022.

American Heart Association. High blood pressure, pregnancy complications may greatly raise future moms' heart risk .

American Heart Association. Health threats from high blood pressure .

American Heart Association. Types of blood pressure medications .

American Heart Association. Changes you can make to manage high blood pressure .

American Medical Association. 7 steps women should follow to improve blood pressure control . October 16, 2023.

American Heart Association. Hypertensive crisis: When you should call 911 for high blood pressure.

By Rachael Zimlich, BSN, RN Zimlich is a critical care nurse who has been writing about health care and clinical developments for over 10 years.

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THE WPATH TAPES: Behind-Scenes Recordings Reveal What Top Gender Doctors Really Think About Sex-Change Procedures

Megan Brock / @MegEBrock / Kate Anderson / @kliseanderson / May 15, 2024

Recordings from meetings of the World Professional Association for Transgender Health reveal doctors pushing risky sex-change procedures for children, contradicting the organization's own guidelines. (Photo illustration: Anastassiya Bezhekeneva/Getty Images)

Get your FREE digital copy of The Heritage Foundation’s Founders’ Almanac.

The World Professional Association for  Transgender Health , or WPATH, is the leading authority in the field of gender medicine. Its guidance is routinely used by top medical associations in the U.S. and abroad, while its standards of care inform insurance companies’ approach to coverage policies.

But behind closed doors, top WPATH doctors discussed, and at times seemed to challenge, the organization’s own published guidelines for sex-change procedures and acknowledged pushing experimental medical interventions that can have devastating and irreversible complications, according to exclusive footage obtained by the Daily Caller News Foundation.

WPATH published highly influential clinical  guidance  called “Standards of Care for the Health of Transgender and Gender Diverse People, Version 8,” or SOC 8, which recommends the use of invasive medical interventions such as puberty blockers, cross-sex hormones and sex change surgeries, calling them “safe and effective.”

The Daily Caller News Foundation filed a series of public records requests to the World Professional Association for Transgender Health’s SOC 8 co-authors who are employed at taxpayer-funded institutions, making their emails subject to open records laws.

Buried in more than 100 pages of responsive records from the University of Nevada was a series of emails sent in 2022 among prominent WPATH members and leaders , including WPATH Global Education Institute Co-Chair Gail Knudson.

In one email, Knudson sent a colleague the link to a folder containing nearly 30 hours of recordings from WPATH’s Global Education Institute summit in September 2022 in Montreal, Canada, which included sessions on mental health, puberty blockers, cross-sex hormones, and sex-change surgery.

These sessions provided WPATH members with in-depth education on the clinical application of topics addressed in the SOC 8 treatment guidelines. However, the footage reveals WPATH-affiliated doctors advocating that children undergo risky sex-change procedures and even pushing for these treatments for patients struggling with severe mental health issues.

Several sessions were dedicated exclusively to treating children and included recommendations for minors to receive puberty blockers, cross-sex hormones, and surgeries.

For instance, WPATH guidance recommends addressing a patient’s mental health issues before giving him or her sex-change medical interventions. However, in one recorded session, a WPATH faculty member and gender doctor claimed that mental health issues don’t necessarily affect a patient’s ability to receive cross-sex hormones.

In another video, a doctor told attendees that children should be informed that cross-sex hormones will likely make them infertile. but admitted that he would prescribe them anyway if a child says he or she wants the treatment, regardless of future consequences.

A surgeon euphemistically referred to a phalloplasty procedure, a surgical series that includes obliterating the vaginal cavity and creating a fake penis with harvested tissue, as an “adventure” for young people. He did this despite later admitting that those same procedures “definitely” will have “complications,” such as permanent issues with bladder function and tissue death.

One physician called the entire field of cross-sex hormones “off-label,” referring to the concept of drugs being used for alternative purposes than what they were approved for. The doctor went on to say that female patients might actually appreciate drug side effects that cause them to lose hair, because they’d look “more like men.”

The U.S. Food and Drug Administration  says  that when it approves a drug, health care providers generally may prescribe that drug for an unapproved use, or off-label, when “they judge that it is medically appropriate for their patient.”

In several other videos, doctors argued in favor of transitioning patients who experience psychotic episodes. One admitted that some of his patients with schizophrenia have to be careful how much cross-sex hormones they take or they can’t “keep the voices down.”

The Daily Caller News Foundation consulted medical professionals from respected organizations, such as Do No Harm, who all argued that the comments from WPATH-affiliated doctors show that the transgender medical industry doesn’t have patients’ best interests at heart.

While the average person, nationally and internationally, likely never has heard of the World Professional Association for Transgender Health, the modern medical industry is deeply tied to the organization and relies on it to dictate the standards of care for transgender medicine.

WPATH’s guidelines are cited as criteria for obtaining insurance coverage by both  private insurance companies  and tax-funded  insurance plans , positioning them as a lynchpin of the sex reassignment industry.

Additionally, WPATH’s guidelines help inform policy statements from major medical and professional organizations, such as the  American Academy of Pediatrics , the  American Psychological Association , and the  Endocrine Society .

The American Academy of Pediatrics is being sued by Isabelle Ayala, a former patient who was medically transitioned as a child and claims she was rushed through sex-change medical procedures.

There’s been an explosion in the number of young people, including children, being put on hormones and puberty blockers and getting sex-change surgeries, according to a study published in August 2023 by the JAMA Network.

This surge has been fueled, in part, by groups such as Planned Parenthood, which distributes cross-sex hormones to patients as young as 16. Planned Parenthood  saw  a roughly 125% jump in the number of transgender services it provided between 2020 and 2022.

Twenty-three states, however, have  enacted  legislation preventing doctors from performing sex-change surgeries on minors amid backlash from concerned parents and doctors who don’t subscribe to the WPATH-endorsed “gender-affirming care” model. Gender-affirming care is another euphemism used by medical professionals to describe the idea that doctors should affirm a patient’s wish to live as the opposite biological sex through social transitioning, hormone therapy, and even surgery.

The SOC 8 was released just days ahead of the 2022 symposium and contained several significant changes to how doctors and medical institutions implemented transgender medical treatment. For instance, WPATH removed minimum age requirements that established when a child can or should receive transgender medical services such as puberty blockers, cross-sex hormones, and sex-reassignment surgeries.

The World Professional Association for Transgender Health’s previous guidelines recommended that hormone therapy be given once a patient was over the age of 16, but the updated version removed this barrier and suggests hormone therapy begin at the first signs of sexual maturity.

The videos obtained by the Daily Caller News Foundation give the first glimpse at how doctors and mental health professionals discussed implementing the new guidelines. To highlight the most significant portions of the content obtained in the records requests, the foundation has decided to publish a series of articles collectively called “The WPATH Tapes.”

Following this release, the Daily Caller News Foundation intends to publish all of the videos in their entirety to provide the public with necessary information about WPATH’s approach to medical care and shine a light on an influential organization that has largely remained anonymous until now.

“The WPATH Tapes” Table of Contents

• Video Shows Prominent Doctors Acknowledging, And Even Challenging, The Experimental Nature Of Sex Change Drugs
• Top Psychiatrist Argues Schizophrenic Patients Can Consent To Sex Change Surgeries
• ‘Keep The Voices Down’: In Unearthed Video, Doctors Discuss Putting Mentally Ill Patients, Including Kids, On Hormones
• Gender Doctor Calls Genital Surgery An ‘Adventure’ For Young People While Describing Grisly Complications
• ‘No Idea About Their Fertility’: Gender Doctors Shed Light On Grim Reality Facing Kids Considering Sex Changes
• Leader Of Gender Medicine Org Says Binary Sex ‘Doesn’t Really Hold True,’ Cheers On ‘Deconstructed’ Biology
• Private Footage Reveals Leading Medical Org’s Efforts To ‘Normalize’ Gender Ideology

Originally published by the Daily Caller News Foundation

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Watch CBS News

DeSantis signs flurry of anti-trans bills, including ban on gender-affirming care for minors

By Aaron Navarro

May 17, 2023 / 9:41 PM EDT / CBS News

Florida Gov. Ron DeSantis signed several anti-transgender bills Wednesday which ban gender-affirming care for minors, ban children from attending drag shows, and target how students learn about and engage with the LGBTQ+ community. 

Senate Bill 254 outlaws gender transition surgeries and medication, such as puberty blockers, for minors. It also makes it a first-degree misdemeanor for physicians and health care workers to provide gender-affirming medication or conduct these surgeries, and gives state courts the ability to obtain a warrant to take physical custody of a child who is "being subjected to sex-reassignement prescriptions or procedures."

DeSantis also signed an expansion of the Parental Rights in Education bill , which prohibits the instruction of sexual orientation and gender identity. The bill, initially signed into law in March 2022, applied to students in third grade and under. But with the expansion, it now applies to those in eighth grade and under. 

The expansion, House Bill 1069 , also defines in the state's education code that "sex" is either male or female, and that teachers can't be required to use a child's or co-worker's preferred pronouns "if such personal title or pronouns do not correspond to that person's sex."

It's an action that Republicans argue promotes parental involvement in education, while LGTBQ+ advocacy groups say it promotes unjust censorship and is discriminatory towards the communities they represent.

Other bills signed Wednesday include bans on minors from attending drag shows, strip clubs or other "sexually explicit adult performances," and a bill titled "Ensuring Women's Safety," which bans trans people from using restrooms, locker rooms or other public facilities that match their identified gender. 

Florida is one of at least 19 Republican-led states that have banned youth gender transition surgeries or other forms of gender-affirming care, including Arizona, Missouri, Georgia, Montana and Iowa, according to the Human Rights Campaign . 

Trans youth between the ages of 13 and 17 make up about 1.32% of that age group's population in Florida, according to numbers tracked by the Williams Institute at the University of California-Los Angeles School of Law.

In a bill signing ceremony Wednesday, DeSantis said the expansion of the Parental Rights in Education bill "crucially makes sure that Florida students and teachers will never be forced to declare pronouns in school or be forced to use pronouns not based on biological sex." 

"We never did this through all of human history until like, what, two weeks ago? Now, they're having third graders declare pronouns. We're not doing the pronoun Olympics in Florida," DeSantis said. 

"If a parent wants to engage in that with their kid at those ages, then that's up to them, but we should not be putting that in the curriculum in schools," DeSantis added. 

Florida state Sen. Clay Yarborough, a Republican who authored the expansion — and who on Wednesday endorsed a 2024 presidential run by DeSantis — told CBS News earlier this month that the bill was encouraged after hearing from parents about sexual orientation being taught in middle schools. 

"We still had non-compliance with current law, like materials in the library that were pornographic," Yarborough said. "If we can't show certain content on a nightly newscast … why would we let fourth graders sit in the corner of a library to look at that?"

"We're not saying you can't learn about these topics at all, we're saying parents need to be in the driver's seat," he added.

In response to the bills, Human Rights Campaign President Kelley Robinson said that DeSantis "has made clear that demonizing LGBTQ+ people will be the center of his legislative agenda and presidential run." 

"The rights of millions of Floridians are being rolled back by politicians who are attacking the LGBTQ+ community at a breakneck pace to pander to the most extreme fringes of their base," she said in a statement. 

Joe Saunders, a former Democratic state lawmaker who is now the senior political director at the Equality Florida group, argued that the numerous anti-LGBTQ+ bills passed during this session are being used by DeSantis to appeal to Republican primary voters in a potential 2024 presidential run. 

"His ambition and his extremism is ruining Florida," he said. "It's clear that the DeSantis political machine has decided that attacking the parents of LGBTQ kids … attacking drag queens, who are just trying to make a living, is somehow part of the math for that."

Saunders pointed to impacts from the version of the Parental Rights in Education bill passed last year — such as the Miami-Dade County Public School Board striking down a resolution to recognize LGBTQ history month — despite passing a resolution to do so before the law went into effect.

Anti-trans rhetoric, particularly as it relates to education and school sports, have been a frequent topic in DeSantis' out-of-state political speeches in recent months. 

"It is wrong for a teacher to instruct a student that they were born in the wrong body, or that their gender is a choice. We should not have transgender ideology in our schools, and in Florida, we have eliminated it," DeSantis said at a fundraiser in Sioux Center, Iowa last Saturday. He added that youth gender transition surgeries are "barbaric."

— Ed O'Keefe contributed reporting. 

• Transgender
• Ron DeSantis

Aaron Navarro is a CBS News digital reporter covering Florida Governor Ron DeSantis' presidential campaign and the 2024 election. He was previously an associate producer for the CBS News political unit in the 2021 and 2022 election cycles.

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• v.10(3); 2022

Gender Dysphoria and Its Non-Surgical and Surgical Treatments

Danyon anderson.

1 Medical School, Medical College of Wisconsin

Himasa Wijetunge

2 School of Medicine, Louisiana State University Health Sciences Center

Peyton Moore

3 School of Medicine, Louisiana State University Health Science Center

Daniel Provenzano

Jamal hasoon.

4 Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School

Omar Viswanath

Alan d. kaye.

Gender dysphoria is defined by severe or persistent distress associated with an incongruence between one’s gender identity and biological sex. It is estimated that 1.4 million Americans and 25 million people worldwide identify as transgender and that 0.6% of Americans experience gender dysphoria. The pathophysiology of gender dysphoria is multifactorial and incompletely understood. Genetics, androgen exposure, neuroanatomy, brain connectivity, history of trauma, parents with psychological disorders, and being raised by less than two parents are associated with gender dysphoria. Gender dysphoria most frequently presents in early teenage years but can present earlier or later. Anxiety and depression are the two most common comorbid diagnoses and may be the reason for presentation to medical care. Diagnosis is established through history and or validated questionnaires. Treatment includes psychosocial therapy, pharmacotherapy for underlying depression and/or anxiety, hormonal therapy, non-genital and/or genital feminization or masculinization operations. The frequency and severity of treatment related morbidity increases progressively as treatments go from conservative to more invasive. Gender dysphoria and its treatment is individualized and not completely understood.

Introduction

Gender dysphoria, also known as gender incongruence, is a condition that occurs when an individual’s gender identity differs from their biological sex. This condition can cause severe physical and psychological stress.

One recent report finds that 1.4 million individuals or 0.6%, of the adult U.S. population identifies as transgender. 1 Another meta-analysis finds that prevalence is drastically different depending on how transgender is defined. There is a higher prevalence of people who self-report as transgender than there are of patients who are being treated for gender dysphoria. 2,3

The pathophysiology of gender dysphoria is something under active investigation. There are twin studies with small sample sizes that demonstrate a genetic component of gender identity. 4 There is also evidence of neuroanatomical differences among transgender individuals. 5–7

A diagnosis of gender dysphoria can be made if a patient is experiencing gender incongruence that causes significant distress. Individuals typically present with gender dysphoria during adolescence, but it is not uncommon for patients to present in early childhood or after the age of 18. 8,9

Patients with gender dysphoria who receive treatment report happier lives. There is also a decreased rate of suicidality among patients who receive appropriate gender affirmation treatment. 10 Treatment starts with hormone therapy. Patients who have received hormone therapy for a year may qualify to undergo gender confirmation surgery. Adverse effects of certain treatments, especially surgical, can be significant.

This review paper aims to update the reader on the most recent research of all aspects of gender dysphoria.

Epidemiology

It is estimated that there are 25 million transgender people worldwide. 11 Determining the prevalence of gender dysphoria and transgenderism is difficult as it varies based on the definition used. For example, there is a much higher prevalence of people who self-identify as transgender compared to people who have received hormone therapy or gender affirmation surgery. 2,3 Exact prevalence is difficult to quantify due to differences among geographical areas. One report shows that the prevalence among the total U.S. population is about 0.6%, but if broken down by state, it varies from 0.3%-0.76%. 1 This also holds true when comparing epidemiological studies of gender dysphoria across different countries. 3,12 Recent data shows that there has been an increase in the prevalence of individuals seeking treatment for gender dysphoria. 13 The aforementioned report shows that the prevalence of Americans identifying as transgender has doubled over the last 10 years. 1 The biggest increase is among children and adolescents. 14 It is unclear if this is due to an actual increase in the number of individuals with gender dysphoria or a societal shift towards openness and acceptance of variations in gender identity. Prior to the overall increase in prevalence, the sex ratio once favored birth assigned males to, now, favoring birth assigned females. 15 Recent data also suggests that individuals typically experience their first gender dysphoria symptoms by age 7 and often live for over 20 years before seeking treatment. 16

Pathophysiology/Risk Factors

There is growing evidence for a broad biological basis of gender identity. A variety of studies show evidence of genetic links, neuroanatomical differences, and prenatal androgen exposure that affect gender identity. Data in this field is more recent, as older studies mostly focused on psychosocial aspects of gender identity and gender dysphoria.

Genetic evidence is based on studies of sex hormone signaling genes and twin concordance studies. Foreman et al. finds statistically significant genetic differences in sex signaling genes in transgender women compared to cisgender males. These differences include differences in alleles, genotypes, and allele combinations mostly involving androgen receptor genes. 17 There are many, mostly small, twin heritability studies of gender dysphoria with a recent review showing that most estimates of heritability fall in the range of 30-60%. 18 Combined, this data supports a polygenic component of gender identity.

Neuroanatomical studies show the brains of gender dysphoric individuals resemble the gender they identify with as opposed to those of the gender they were assigned at birth. Studies in this field are mainly neuroimaging studies that find increased cortical thickness, and weaker connections in regions of the brain known for processing one’s own body perception. 5–7 More recently, brain connectivity studies find that brain connectivity dynamics are similar among transgender individuals and the gender they identify with than with the gender they were assigned at birth. 19 While more studies need to be done to further elucidate the neuroanatomy and neurophysiology, the current research suggests that brain architecture and function play an important role in gender identity and gender dysphoria.

It is well established that androgens play a crucial role for the development of sex characteristics, sexual, and gender identity. 20,21 Studies show that women exposed to high levels of androgens due to congenital adrenal hyperplasia (CAH) are more likely to be dissatisfied with their gender assigned at birth. 20 On the other hand, patients with complete androgen insensitivity (CAIS) typically express female gender identification. 22 These individuals are XY, but develop female secondary sexual characteristics, and most often identify as females. This occurs due to androgen receptor defects which lead to androgen resistance. CAIS patients also have undescended male testis which cause them to have male levels of testosterone. Data from these patients shows a clear link between androgen exposure and gender identity.

There are also psychosocial factors that are associated with gender dysphoria. Early researchers hypothesized that gender dysphoria development was due to certain parental influences such as lack of paternal reinforcement and paternal absence among other factors. Some of these hypotheses have been tested but the data are not conclusive. 23,24 More recent data show that elevated levels of psychopathology in parents and childhood anxiety increase risk for development of gender dysphoria. 25,26 Overall, studies on the psychosocial factors of gender dysphoria are older and more scarce than recent data on the biological factors regarding gender identity.

Clinical Presentation and Diagnosis

Gender dysphoria has become progressively more common and has been recognized and treated earlier over the last two decades. 27 The presentation and diagnosis of these individuals can often be a challenge due to the sensitive nature of the topic. These individuals often present in their adolescent and teenage years when their gender identity. 28 In studies of adolescents done in China, there was a high correlation between those who identified as transgender and non-binary and high scores on the generalized anxiety disorder scale as well as the suicidal ideation assessment. Early detection of adolescents with gender dysphoria helps establish psychiatric treatment of comorbid depression and anxiety. 29 The Diagnostic and Statistical Manual for Mental Disorders 5 th edition (DSM-5) defined two criteria for the diagnosis of gender dysphoria in adolescents. The first is defined by “A marked incongruence between one’s experienced/expressed gender and assigned gender, of at least 6 months’ duration, as manifested by at least two of the following:

• a marked incongruence between one’s experienced/expressed gender and primary and/or secondary sex characteristics (or in young adolescents, the anticipated secondary sex characteristics);
• a strong desire to be rid of one’s primary and/or secondary sex characteristics because of a marked incongruence with one’s experienced/expressed gender (or in young adolescents, a desire to prevent the development of the anticipated secondary sex characteristics).
• a strong desire for the primary and/or secondary sex characteristics of the other gender.
• a strong desire to be of the other gender (or some alternative gender different from one’s assigned gender).
• a strong desire to be treated as the other gender (or some alternative gender different from one’s assigned gender).
• a strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender different from one’s assigned gender)“.

The second criteria states that “The condition is associated with clinically significant distress or impairment in social, occupational or other important areas of functioning”. 30 Most often these adolescents present during the early stages of puberty with incongruence between sex assigned at birth and gender identity. 31 This can present as many different behaviors such as changing one’s hair, clothing, behaviors, or name to match their preferred gender. Distress can be observed as outbursts against parents or peers who may attempt to make the child conform to their birth sex. 32 Distress may also present as the child being resistant towards going to school through means of pretending to be sick. Distress may also present as signs of physical abuse from bullying such as bruises or scrapes. 27 Studies done in Germany showed that 26% of patients that presented to the clinic with gender dysphoria endorsed negative responses to their outings at school. 33 Comorbid depression and anxiety might also prompt patients to present to clinic, and further questioning is often required to reveal underlying gender dysphoria. 28 Treatment of underlying anxiety and depression is important in individuals who suffer from gender dysphoria as they have been shown to have higher rates of attempted and completed suicide compared to cis-gender counterparts. Studies also show that individuals who received gender-affirming treatment at younger ages had less suicidal ideation than those who received treatment later. 34 While it is most common for gender dysphoria to present in early teenage years, it is not uncommon for individuals to present in early adulthood. Almost 25-30% of patients with gender dysphoria present after the age of 18. In many of these cases, pressures from peers and family often delays presentation and treatment. 35 Another common risk factor for individuals with gender dysphoria is a history of childhood trauma. A survey conducted of 95 transgender individuals who previously self-reported having symptoms of gender dysphoria showed that 56% of these individuals experienced four or more early traumatic events in their childhood. Most often, these experiences were physical or emotional abuse from parents. Trans women had more events involving physical and psychological abuse from their father while being separated from their mothers. Trans men had more events involving their mothers and were frequently separated from and neglected by their father. 36 Studies have also shown that children who experience trauma early in life are more likely to develop disorganized attachments. This makes children more likely to develop dissociative and avoidant strategies for dealing with complex emotions and thoughts such as gender identity incongruence. Children and adolescents with significant history of trauma present later and are less likely to present to clinicians for evaluation. 37

Several tools have been developed to help clinicians diagnose gender dysphoria. These tools include self-surveys that can be given to patients to assess thoughts and symptoms of gender dysphoria. The most common and well-studied of these questionnaires is the gender identity/gender dysphoria questionnaire for adolescents and adults (GIDYQ-AA). This questionnaire has been verified to aid in the identification of individuals with gender dysphoria. The questionnaire has a sensitivity of 90.4% in the 73 transgender patients and a 99.7% specificity for the control group which included 389 university students that were both heterosexual and homosexual. 37 Additionally, the generalized anxiety disorder assessment (GAD-7) and the patient health questionnaire (PHQ-9) should be used in all adolescents, but this is particularly important in patients with gender dysphoria due to their higher incidence of anxiety and depression. 33 Many other tools have been recently developed to help diagnose and assess gender dysphoria. The gender identity reflection and rumination scale was developed to assess how often a person thinks about their gender identity. Higher scores correlated to more thoughts on gender identity which in turn correlated to higher frequencies of gender dysphoria. 38,39 Another aspect of the prognosis of adolescents with gender dysphoria is their sense of belonging they feel with their home community. Many studies have shown that trans-gender individuals who feel accepted in their communities or home have lower incidences of comorbid anxiety, depression, and suicide than those who are raised in communities where they feel mistreated. 40

The treatment for gender dysphoria is often multi-disciplinary, combining the efforts of several behavioral health and medical professionals. The World Professional Association for Transgender Health (WPATH) has developed recommended standards of care for treatment, and it’s clearly stated that these standards are “flexible” clinical guidelines. 41 The importance of this flexibility is to ensure individuality in treatment, as each patient may present with different goals or needs. The treatments can be divided into two main categories: non-operative and operative. Non-operative treatment focuses on implementing psychosocial therapy and/or medical management with hormone replacement therapy. Operative treatments range from small cosmetic procedures to much larger genital transformation surgeries. It is important to consider that an individual’s overall treatment may require a combination of both operative and non-operative practices.

Non-Operative Treatment: Psychosocial Therapy

Of the many recommended treatments for gender dysphoria, the first non-operative option is psychosocial therapy and counseling. The overall goal of psychosocial therapy is to improve the patient’s quality of life through open and consistent communication. 41 There are numerous aspects to this, but the objective is to support patients as they begin to implement their gender identity to their loved ones and society. Mental health professionals provide support by answering questions and discussing body image regarding the society-based gender normative. In addition, these professionals guide patients with coming out to friends, family, and colleagues. 42 The true benefit to therapy is that it is ongoing, rather than a single experience; patients can utilize this support lifelong, which is a key component to maintaining positive outcomes. For those who may not have access to a mental health professional, numerous support systems exist, including peer groups and internet-based support groups. 43 The WPATH recognizes that psychotherapy successfully helps individuals with their gender identity without needing hormone based medical therapy or gender affirmation surgery. 41,42

Non-Operative Treatment: Hormone Replacement Therapy

The second non-operative treatment option is medical management with hormone replacement therapy (HRT). According to the WPATH, numerous hormone combinations have been used in the treatment of gender dysphoria, however the data lacks an established standard regiment. 41 HRT requires a very in-depth pre-treatment work-up, which includes risk screening, thorough history and exam, as well as numerous laboratory studies to evaluate the patient’s ability to safely tolerate hormone replacement. 44 Some aspects of this pre-treatment work-up include medical and family history accessing for previous cardiovascular or thromboembolic disease, exam findings including weight, blood pressure, and secondary sexual characteristics, and finally laboratory testing focused on blood, liver, and current hormonal function. 45 It is imperative to confirm the diagnosis and ensure that a written indication for HRT is established by a psychotherapist or psychiatrist. 44 The goal of hormone replacement therapy is to promote the characteristics of the patient’s desired gender while minimizing the characteristics of their biological gender. 42

We will first discuss feminizing therapy for male-to-female (MTF) gender dysphoria. Feminizing HRT generates the following effects on the genetically male body: it softens the skin, decreases body hair production, reduces muscle mass, reduces testicular size, and encourages breast growth. The onset of these effects may begin within 6 months, while the maximum effects are expected to take place between 1-2 years. 41,45,46 These effects are achieved with a combination of pro-estrogen and anti-androgen therapy. Several sources suggest that treatment with physiologic doses of estrogen alone is insufficient to suppress testosterone to the level of a normal female, hence the addition of anti-androgen therapy is needed. 46,47 Pro-estrogen therapy involves the oral or transdermal administration of 17β-estradiol, which activates estrogen receptors and produces the effects listed previously. The recommended anti-androgen therapy is spironolactone, which is an androgen receptor antagonist that is very effective at inhibiting the actions of testosterone; it also has some estrogenic activity. 48 Supplementing synthetic estrogen has its risks, and it is very important for clinicians to monitor serum estradiol levels routinely every 3 months. Although the risk of adverse effects is controversial, the data supports that elevated levels of blood estrogen may lead to increased risk of liver disease, cardiovascular disease, hypertension, hyperprolactinemia, hypertriglyceridemia, and thromboembolic events. 41,44,45,49

The next discussion will be on masculinization therapy for female-to-male (FTM) gender dysphoria. This treatment is generally less complex than MTF therapy. Here, the primary hormone supplemented is testosterone. Several medications are available, which include testosterone enanthate and testosterone cypionate. These two specifically are administered via intramuscular injection, but other options are available that are administered via transdermal gels or patches. Administering testosterone activates androgen receptors which produces the following effects on the genetically female body: increased skin oiliness, increased facial and body hair production, increased muscle mass/strength, redistributed fat, halted menses, deepened voice, enlarged clitoris, and vaginal atrophy. 50,51 With FTM therapy, supplementing with testosterone provides individuals with the desired body changes. Anti-estrogen therapy is not needed to achieve the physiologic levels of testosterone in the normal male. This is what makes FTM therapy less complex than MTF therapy. 41,46 With testosterone supplementation, the adverse risks to screen and monitor for include erythrocytosis, liver disfunction, cerebrovascular disease, coronary artery disease, and breast or uterine cancer. 44,46,47,49

Operative Treatment

Many patients with gender dysphoria require some form of surgery to fully achieve their desired body image and psychological gender identity. These procedures, both genital and non-genital, are collectively known as “Gender Confirmation Surgery” (GCS). Genital surgeries specifically are often the last recommended as part of the overall treatment of gender dysphoria. This is due to permanent alteration in fertility, as well as the risks that are associated with surgery in general. When applicable, GCS can be utilized by health care experts to enhance patients’ gender identities in ways that psychotherapy and HRT may not be able to. 42,52 The WPATH recommends patients undergo some form of social transition utilizing psychotherapy and HRT prior to considering surgical treatment, but it is not a requirement for all procedures. 1 However, the WPATH has specific criteria for genital GCS, and this includes having at least 2 referrals from separate medical health professionals and complete patient compliance with at least 12 months of continued HRT. It is important to note that GCS is performed by many surgical fields, including plastic surgery, urology, otolaryngology, gynecology, and general surgery. 41,52

Operative Treatment: Non-Genital Feminization

There are several methods in which transgender women can surgically enhance their body image. The following are some of the procedures available: hair reconstruction and removal, voice modification, lipofilling, botulin toxin injections, mammoplasty, breast augmentation, gluteal augmentation, waist lipoplasty, and facial plastics. Facial plastics is the most sought after and contains an extensive array of options for patients. Some of the procedures that specifically fall under facial plastics include lip filler, face lifts, rhinoplasty, sinus surgery, forehead cranioplasty, supraorbital ridge reduction, mandibular reduction, and genioplasty. 50,53,54 There are several sources confirming that patients who undergo non-genital feminization surgery have high satisfaction rates and these procedures are often more desired compared to genital reconstruction surgery. 41,42,49,54

Operative Treatment: Genital Feminization

The most important aspect to determining which type of genital feminization surgery a patient desires is whether the patient is wanting penetrative ability. If an individual desires just the feminine appearance without penetrable ability, the recommend procedure would be a bilateral orchiectomy with a penectomy and urethroplasty. The orchiectomy would remove the main source of endogenous testosterone production, while the penectomy and urethroplasty would remove the penis and leave a proper functioning urethra. If a natural appearing vulva without penetrative ability is desired, then the recommended surgery here would be a vulvoplasty with clitoro-labioplasty. Finally, if a patient desires the natural vulva appearance with penetrative ability, an even more complex procedure is recommended. Here, the surgeon would perform the previously mentioned procedures with the addition of a vaginoplasty. 52 The vagina would be created either by inverting the penile skin or utilizing an intestinal graft while the vulva will be shaped using various skin graft techniques. 55 There are numerous complications that may arise from these invasive procedures. The more prevalent complications include neovaginal bleeding, discharge, introital stenosis, misdirected urinary stream, urinary incontinence, would healing disorders, and infection. 56–58

Operative Treatment: Non-Genital Masculinization

As compared to feminization surgery, there are fewer non-genital procedures performed for masculinization. The most popular and sought-after procedures involve masculinizing the chest which consists of subcutaneous mastectomy, chest contouring, pectoral implanting, and breast augmentation. For facial plastics, the most performed masculinization procedures are genioplasty, liposuction, and facial hair transplantation. 42,44,52,55 As with feminization, these non-genital masculinization procedures have high satisfactory rates from patients when combined with the additive effects HRT produces. 41,42,49,54 This is likely due to HRT for masculinization providing enough of an effect to reduce existing feminine characteristics.

Operative Treatment: Genital Masculinization

For genital altering masculinization, many transgender males prefer to start with removal of their biological reproductive organs. This consists of a complete hysterectomy, oophorectomy, and vaginectomy. Doing so permanently eliminates fertility and terminates menstruation; the termination of menstruation is one of the most desired outcomes. To achieve standing micturition, transgender males may undergo urethral lengthening. If the appearance of external male genitalia is desired, more complex procedures are required, such as metoidioplasty or phalloplasty with a scrotoplasty. The combination of these procedures allows transgender males to fully replicate external male genitalia. 58,59 As with feminization genital surgery, similar risks and complications exist with masculinization genital surgery which include including urinary incontinence, would healing disorders, and infection. 42,56,59

In recent decades, changes in the acceptance of variations in gender identity have facilitated more individuals openly expressing themselves as transgender. This is evident by the increasing number of people who identify as transgender over the past decade. 1 There is also an increasing body of evidence of a biological basis of gender identity. The rate of increase of prevalence of transgender individuals has been highest among children and young adolescents. 14 These patients will often first present to their primary care providers (pediatricians in this case) with either complaints of depression or anxiety from suffering with their identity crisis, or questions or desire about gender transition treatment. Treatment decreases suicidality among individuals with gender dysphoria and leads to improved quality of life. 10 Treatment options include psychosocial therapy, medical treatment for underlying depression and/or anxiety, hormonal treatment, and more than a dozen possible surgical procedures. More invasive treatments are associated with more severe adverse effects. Gender identity research is increasing rapidly, but there are still gaps in knowledge. Also, there is a need for large studies of long-term health outcomes of transgender individuals receiving medical and/or surgical treatment for gender dysphoria. Overall, this review paper provides the most up to date information regarding gender dysphoria and its treatments.

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England set to ban gender identity teaching in schools

The measures are to ensure children are 'not exposed to too much too soon', said education minister Gillian Keegan © Daniel LEAL / AFP

The move follows a landmark review which last month urged "extreme caution" on prescribing hormone treatments for young people grappling with gender identity issues.

England's first gender identity development service for children, run by the Tavistock and Portman NHS Trust, closed in March after years of criticism that it had been too quick to prescribe puberty-blocking treatment.

Under the proposals contained in the new draft guidance, the "contested theory of gender identity" would not be taught to pupils of any age, said a Department for Education statement.

Education Secretary Gillian Keegan said the measures were aimed at making sure children were "not exposed to too much too soon, taking away the innocence of childhood.

"That is why this updated guidance includes clear age limits for the teaching of the most sensitive content and specifies that the contested topic of gender identity should not be taught," she wrote in the guidance document.

- 'Toxic' debate -

Since 2020, sex education has been compulsory in secondary schools in England, which teach children from the age of 11.

But the subject, and particularly gender identity, has increasingly become part of the "culture wars" between social conservatives and liberals.

Harriet Cass, the retired paediatrician who led the four-year review into gender identity services, called the "toxicity" of the debate "exceptional".

"At secondary school (11-18 years) pupils will learn about legally 'protected' characteristics, such as sexual orientation and gender reassignment," said the Department for Education statement.

"But the updated guidance is clear that schools should not teach about the concept of gender identity."

- 'Inappropriate' content -

The proposals will also ban sex education for children under the age of nine following concerns about some of the materials being used in schools.

"Parents rightly trust that when they send their children to school, they are kept safe and will not be exposed to disturbing content that is inappropriate for their age," Prime Minister Rishi Sunak said in the statement.

"That's why I was horrified to hear reports of this happening in our classrooms last year," he added.

The National Association of Head Teachers (NAHT) questioned whether the government's proposals would effectively protect children given the widespread access to smartphones.

"We cannot ignore the fact that some children and young people are already accessing information from different sources outside of school," said the union's general secretary Paul Whiteman.

"This may lead to questions that need careful handling from trained professionals."

- Suicide prevention -

The new guidance also includes additional content on suicide prevention and the risks of viewing content promoting self-harm online.

The extent of harmful material available online was highlighted in the UK by the death in 2017 of 14-year-old schoolgirl Molly Russell.

A coroner ruled that she had died from an act of self-harm while suffering from the "negative effects of online content", leading her family to set up a campaign highlighting the dangers of social media.

Her father Ian Russell last year criticised the response of social media companies to a report aimed at preventing future tragedies as "underwhelming and unsurprising".

The government's new proposals will be subject to a nine-week consultation and be statutory once finalised.

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