Transgender Patients on Hormone Therapy Require Monitoring

Vincent Richeux

November 28, 2022

PAU, France — Transgender patients on hormone therapy have an increased mortality risk, compared with the general population, and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D'Assigny, MD, of the Department of Endocrinology, Diabetes and Dietetics at Poitiers University Hospital, Poitiers, France at the Infogyn 2022 conference. Since transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, "should be deemed high-risk cardiovascular patients, or even very high-risk in some cases," said D'Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of < 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level < 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.

High Mortality Rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4500 people, mostly male to female (MtF) transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC, Holland.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly five decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared with transgender men. "Much is still to be done," said D'Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly due to a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

"These causes of death don't give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients," said the study authors.

"Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women," they added.

People with gender dysphoria who receive no treatment for gender reassignment have a suicide rate of 40%, estimated Madec.

Screening for Osteoporosis

In addition to cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing "when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy," said D'Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2260 transgender women that was carried out by a team at Amsterdam UMC in the Netherlands.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but three times lower than in cisgender women.

The authors noted that "the risk of breast cancer in trans women increases during a relatively short duration of hormone treatment," going on to say that "these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy."

Poorly Attended Screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. "Testosterone causes thinning of the endometrium, which may lead to dysplasia," said D'Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said D'Assigny, which means "we need to raise awareness of their benefit in advance." Vaginal swabs for transgender men and mammograms in transgender women "are resented, on both a physical and emotional level." As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don't always receive appropriate gynecological monitoring, through fear of judgement or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health (HAS) also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

This article was translated from the Medscape French edition.

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