References for this Review were identified through searches of PubMed and Scopus for articles published in English and Spanish from Jan 1, 2000, to April 5, 2016. The search terms used were “transgender”, “transsexual”, or “gender dysphoria” in combination with the terms “testosterone” or “androgen”. Abstracts of articles resulting from these searches and relevant references cited in those articles were reviewed. Case reports and small case series of less than ten individuals were only included
ReviewTestosterone therapy for transgender men
Introduction
Many transgender people seek medical care to obtain hormone therapy for masculinisation or feminisation. The mainstay of treatment is testosterone for a transgender man (also referred to as transman or female-to-male transgender) or oestrogen and antiandrogens for a transgender woman (also referred to as transwoman or male-to-female transgender). However, access to hormone therapy varies greatly by country and many transgender individuals do not choose to pursue hormone therapy. For example, findings from one study in Thailand showed that only 35% of transgender men were taking testosterone and that hormone therapy was often taken without medical supervision.1 Testosterone therapy is typically started after puberty and might be initiated in mid-to-late adulthood for individuals coming to terms with their gender identity later in life.
Over the past few years, awareness and acceptance of transgenderism (also called transsexualism) has substantially increased in many countries, particularly those in western Europe, North America, and Australasia. Nevertheless, there are still many regions of the world where transgender individuals must keep their gender identity hidden due to lack of cultural acceptance, stigma, and overt discrimination. Barriers to receiving culturally competent transgender care are common. In 2015, a representative survey of endocrinologists (n=80) in the mid-Atlantic region of the USA found that 59% did not have any transgender patients under their care, only 50% felt somewhat or very comfortable discussing gender identity or sexual orientation, and 33% did not feel competent to provide transgender care.2
Estimation of the true prevalence of transgenderism is difficult because some transgender individuals come to terms with their gender identity later in life and others do not openly identify as transgender because of societal pressures and stigmatisation. A 1996 study of patients treated at a specialised gender clinic in the Netherlands estimated a prevalence of one in 12 000 men assigned male at birth and one in 30 000 women assigned female at birth.3 In 2010, results from a population-based household probability study of more than 28 000 adults in Massachusetts, USA, showed that one in 215 people identified as transgender.4
Transgenderism has a biological component, as evidenced from anatomical and genetic studies. Data from one anatomical study showed that the volume of the central subdivision of the bed nucleus of the stria terminalis in transgender women was similar to that of natal (also referred to as non-transgender) women rather than non-transgender men.5 Results of a genetics study that included 23 pairs of identical twins and 21 pairs of non-identical twins showed 39% concordance of transgenderism between identical twins and 0% between non-identical twins.6 Nonetheless, the precise genetic foundations of transgenderism are not clear. Investigators have examined several sex hormone-related genes, including CAG repeat length in the androgen receptor gene, CA repeat length in the oestrogen receptor β gene, and TTTA repeat length in the aromatase gene. Although results from some of these studies have suggested an association between transgenderism and particular genetic variations, findings have not been replicated in other studies and the evidence is inconclusive.7, 8, 9
In this Review, I focus on the effects of testosterone therapy on various organ systems in adult transgender men. Because the extent of the effects of testosterone can vary by type of testosterone formulation, this information is included where possible. Where applicable, comparisons will be made with the effects of testosterone therapy in men with hypogonadism and natal women. These comparisons have limitations because of the different host environment in natal men and the lower doses of testosterone that are given to natal women. Importantly, endogenous testosterone concentrations are generally 10–20 times higher in men than in women. Detailed information about the diagnostic criteria for transgenderism or gender dysphoria and general care has been published by the World Professional Association for Transgender Health10 and in clinical guidelines from the Endocrine Society11 and the Royal College of Psychiatrists.12 Table 1 shows a summary of the recommendations and evidence quality from the Endocrine Society's clinical practice guidelines. A major limitation in the study of transgender medicine is a paucity of high-quality data. Difficulties in obtaining such data stem from the scarcity of randomised controlled trials (partly because of ethical issues), few prospective and long-term studies, the use of suboptimum control groups, loss to follow-up, and difficulties in recruitment of representative samples, including people disenfranchised from society and medical care. In this Review I do not address care of transgender adolescents, which may include suppression of the gonadal axis for a period of time before hormone therapy is started.
Section snippets
Overview
The overall goals of testosterone therapy for transgender men are to obtain secondary sexual characteristics of natal men, to live their lives as men, to improve their wellbeing, and to decrease gender dysphoria. Because androgen receptors are widely distributed, testosterone therapy has diverse effects throughout the body, affecting both physical and psychological characteristics (figure). No standard practice exists for starting doses or maintenance doses of testosterone. In clinical
Cardiometabolic risk factors
To provide some context, the cardiovascular benefits and risks of testosterone therapy for natal men with low or low-normal testosterone concentrations are poorly understood and controversial. The cardiovascular effects of testosterone might be mediated via several mechanisms, including changes to insulin sensitivity, lipid profiles, inflammatory cytokines, salt retention, polycythaemia, and platelet aggregation.55 In a 3 year randomised controlled trial that included 308 older men (mean age 68
Conclusions
Within several months of starting testosterone therapy, transgender men begin to notice many desired effects, including increased facial and body hair, increased lean mass and strength, decreased fat mass, deepened voice, increased sexual desire, cessation of menstruation, clitoral enlargement, and reductions in gender dysphoria, perceived stress, anxiety, and depression. The most common undesired effect is acne, for which many patients take topical or oral medications. The main physical
Search strategy and selection criteria
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Breast cancer development in transsexual subjects receiving cross-sex hormone treatment
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Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study
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Hormone-treated transsexuals report less social distress, anxiety and depression
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A single administration of testosterone improves visuospatial ability in young women
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Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women
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