Safety of Physiological Testosterone Therapy in Women: Lessons from Female-to-Male Transsexuals (FMT) Treated with Pharmacological Testosterone Therapy

Abstract

Introduction The safety of long-term physiological doses of testosterone (T) therapy in women with sexual dysfunction is a contentious issue, in part, because of fear of adverse effects, such as breast cancer, vascular disease, and excessive virilization. This unsubstantiated fear has hampered progress in treating women with sexual dysfunction using T therapy in physiological doses to achieve circulating levels in the normal range. Aim To examine evidence derived from studies in female-to-male transsexuals (FMT) treated with supraphysiological (pharmacological) doses of T for long periods of time with no apparent major adverse effects. Methods A comprehensive literature search of relevant articles published between 1980 and 2010 pertaining to the topic of T in FMTs was performed using PubMed. The following key words were used: female-to-male transsexuals; testosterone; virilization; gender re-assignment; and androgen therapy in women. Relevant articles were retrieved, reviewed, and the information was analyzed and evaluated for study methodology and major findings. Main Outcome Measures Data from peer-reviewed publications were critically analyzed and the information was summarized. Results The data from the studies reported in the literature to date strongly suggest that treatment of FMTs with supra-physiological doses of T had minimal adverse effects. No increase in mortality, breast cancer, vascular disease, or other major health problems were reported. Conclusions No significant serious adverse effects were reported in FMTs treated with pharmacological doses of T. In light of the findings with supraphysiological doses of T, we suggest that treatment with T at doses producing physiological levels in women with sexual dysfunction are expected to produce limited and minimal adverse effects.

Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case–control study

“…However, Dhejne et al (4) found that the cause-specific risk of death from neoplasms in trans persons was double that in control individuals, although this was unlikely to be related to cross-sex hormone treatment. Although the incidence of hormone-related cancers was not higher in the trans groups at either short-or medium-term follow-up, the incidence of hormone-related cancers may increase with longer duration of hormone treatment (10).…”

“…However, risks may become more apparent as subjects grow older and the duration of hormone exposure increases (10,25).…”

“…In general, current evidence suggests that testosterone administration in trans men is not very harmful (10), while anti-androgen and estrogen administration may negatively impact cardiovascular health in trans women (2). Both antiandrogens and estrogens increase the risk of venous thrombosis and/or pulmonary embolism (7), and two recent mortality studies have reported a higher cardiovascular mortality rate in trans women than in the general population (4,5).…”

The primary health care of transgender adults

“…33 Among transmen, maintaining physiological male levels of testosterone is protective against osteoporosis. 41 In addition to exogenous testosterone, transmen usually have levels of circulating oestrogen that are likely to be protective against bone disease. The sources of oestrogen among transmen include the peripheral aromatisation of testosterone and ovarian oestrogen production, unless they have been oophorectomised.…”

Long-term cross-sex hormone treatment is safe in transsexual subjects

“…Testosterone treatment is safe in these women and does not lead to increased cardiovascular mortality. 14,15 The fact that testosterone has apparent detrimental effects on surrogate markers of cardiovascular risk 16 but does not increase cardiovascular mortality is, in our opinion, intriguing and certainly calls for wider investigation on the way in which testosterone works in women. 17 Some other important issues remain open and also require further research.…”