Copenhagen, Denmark - New data from a large gender-identity unit have shown that hormone therapy taken by transsexuals is associated with a higher cardiovascular mortality rate among transsexual women (male to female [M2F]) but not men (female to male [F2M]) ¹. Both, however, had a higher incidence of type 2 diabetes than the general population.

"Our main finding concerning hormonal therapy in transsexual persons is that hormonal therapy seems to be safe in transsexual men in the short and middle term (around eight years)," Dr Katrien Wierckx (University Hospital, Ghent, Belgium) said in an interview.

However, "our results substantiate the few other studies published in the past two years, which observed that transsexual women have more cardiovascular diseases compared with the general population. Further research is definitely needed to explore this," she added.

Wierckx and colleagues reported their findings earlier this month, in a poster at the 2013 European Congress on Endocrinology (ECE) meeting.

Wierckx explained that hormone therapy is part of the established treatment of gender-identity disorder, but outcomes data regarding morbidity and mortality "are scant."

In their specialist center, she and her colleagues studied 193 M2F and 128 F2M transsexuals, with a mean age of 42.5 years, assessing physical health and incidence of possible treatment-related adverse effects compared with age-matched female and male control subjects recruited from a population study in Flanders.

M2F transsexuals typically take antiandrogens and estrogens, while F2M transsexuals will receive testosterone therapy. The participants used hormone therapy for 7.4 years on average (range three months to 49 years) and were a mean of 6.6 years from their sex-reassignment surgery.

During follow-up, 10 transsexual persons (9 M2F and one F2M) died. Causes of death were cardiovascular disease (n=2), cancer (n=2) and suicide (n=6).

Three percent of transsexual women (n=10) experienced venous thrombosis and/or pulmonary embolism during hormonal therapy, half of which occurred during the first treatment year (n=5), while another three episodes occurred at the time of sex-reassignment surgery.

Transsexual women also experienced more MI compared with control women (p=0.001), but not with control men. Prevalence of cerebrovascular disease was also higher in transsexual women compared with control men and women (p=0.05 and p=0.02, respectively).

Transsexual men had similar morbidity rates of MI and cerebrovascular disease compared with the control population, however.

Transsexual men also had fewer cancers than the general population, said Wierckx, but she explained this was a result of fewer gynecological malignancies, as breast tissue, uterus, and ovaries are removed during sex-reassignment surgery. But otherwise, there was an equal prevalence of cancer among the transsexual and control population.

And although the incidence of type 2 diabetes was higher in both sexes, all but one diagnosis in transsexual women was found before the start of hormonal therapy, suggesting overdiagnosis, they note. Transsexual men did have a higher incidence of type 2 diabetes compared with the general population, however.

Other research presented at the ECE meeting appeared to demonstrate worsening lipid profiles in F2M transsexuals following testosterone therapy.

Dr Antonia Becerra (Hospital Universitario Ramon y Cajal, Madrid, Spain) and colleagues studied 50 F2M transsexuals following three years of testosterone therapy ². Participants experienced significant reductions in HDL cholesterol and apolipoprotein A-I (apoA-1). They also had significant increases in total cholesterol, LDL cholesterol, apoB, and homocysteine.

However, lipoprotein (a) (Lp[a]) was also significantly reduced, and there were no changes in other components of the metabolic syndrome, Becerra and colleagues noted.

Similarly, Dr Carmen Quir ó s L ó pez (Hospital Clinic Universitari Barcelona, Spain) and coworkers reported on 92 F2M transsexuals after 24 months of testosterone treatment. They experienced a significant increase in weight and body-mass index (BMI) and a worsening lipid profile, with increased total cholesterol, triglycerides, and LDL cholesterol, as well as a decrease in HDL cholesterol.

In 143 M2F transsexuals, however, the Spanish doctors saw no significant changes in lipid profile following hormone therapy, although these individuals did put on weight and increase BMI significantly.

Wierckx and colleagues found similar metabolic results in a separate prospective study conducted with other European gender identity centers. They reported on 24 F2M and 56 M2F transsexuals after the first year of hormone therapy.

"Estrogen and antiandrogens in transwomen lead to more fat mass with a gynoid pattern on distribution. Testosterone treatment induces a less favorable lipid profile in transmen," they conclude.

Wierckx said there are a few possible explanations for this seeming discrepancy, whereby they did not see an increase in cardiovascular events in transmen (F2M) in their larger study, despite reporting unfavorable lipid changes following testosterone therapy in the smaller ongoing prospective trial.

The lipid alterations could "be counterbalanced by a positive effect of other cardiovascular risk factors," she suggested. "For example, it's well-known that fat mass reduces in transsexual men and that they gain muscle mass.

"Another explanation could be that our transsexual men were still too young to experience cardiovascular events, as transsexual men present themselves at younger ages compared with transsexual women."

Cite this article: Hormone therapy associated with MI in male-to-female transsexuals. Medscape. May 14, 2013.

References

• Quirós López C, Patrascioiu I, Mora Porta M, et al. Effect of cross-sex hormone treatment on lipid profile in transsexual individuals: Experience in a specialized unit in Catalonia. 2013 European Congress on Endocrinology; April 29, 2013; Copenhagen, Denmark. Abstract P192

• Van Caenegem E, Wierckx K, Taes Y, et al. Metabolic profile of transsexual persons on cross-sex hormonal therapy in a multi-center prospective intervention study. 2013 European Congress on Endocrinology; April 29, 2013; Copenhagen, Denmark. Abstract P189.