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Current use of testosterone therapy in LGBTQ populations

Abstract

Testosterone therapy (TT) is a type of gender-affirming hormone therapy (GAHT) in lesbian, gay, bisexual, transgender, and genderqueer (LGBTQ) populations for gender dysphoria (GD), body uneasiness, and sexual dysfunction. The physical and physiological effects of TT vary widely depending on the dosing regimen and duration of treatment. An individualized approach prioritizing patient-specific desired effects in the context of pre-existing characteristics and health history is strongly recommended. Although TT is an effective treatment for many patients, there has been an increase in the illegitimate acquisition of TT in recent years. Non-judicious prescribing and lack of physician surveillance increases the risk of unintended side effects and potential serious health consequences.

Introduction

Testosterone (T) is one of the earliest discovered and studied sex hormones [1]. The major functions of T and its androgenic products include development and maintenance of male sexual characteristics, spermatogenesis, musculoskeletal growth, erythropoiesis, and sexual function [2]. TT involves administration of exogenous T, and is classically used for treating androgenic dysfunction in hypogonadal men and postmenopausal women with sexual dysfunction [3, 4]. More recently, TT has increasingly been used for GAHT in LGBTQ populations [5].

Gender identity refers to a person’s inherent sense of being male, female, a combination of both, or neither (referred to as genderqueer) [6]. Gender identity is not synonymous with biological sex, which is assigned at birth. The terms cisgender and transgender describe individuals who’s gender identity and biological sex do or do not align, respectively.

TT is most often used as a treatment for GD, body uneasiness, and sexual dysfunction in LGBTQ populations [7]. According to the DSM-5, GD is a marked incongruence between one’s experienced or expressed gender identity and the gender identity typically associated with their biological sex [8]. Not all members of LGBTQ populations experience GD, however, it is a common source of physical, mental, and emotional distress and is associated with significant impairment of social, occupational, and physiologic functions [8]. The therapeutic goals of TT are patient specific, but may include suppression of natal features, partial masculinization, or transitioning from female to male [7]. As with any pharmacologic agent, there is potential for misuse of TT.

Aim

This review article will focus on TT in LGBTQ populations based on an exploration of existing literature primarily on PubMed and clinical practice guidelines. We will discuss the history of TT and the indications for TT in cisgender men and cisgender women. Then, we will focus on the indications, pros and cons of commonly used T preparations, adverse effects including fertility concerns, and potential for misuse of TT in LGBTQ populations.

History of testosterone therapy

A high demand for testosterone products and financial interest from pharmaceutical companies fueled research that resulted in the successful extraction, isolation, and chemical synthesis of T in 1935 [9]. Introduction of the radioimmunoassay in the 1970s allowed serum T to be measured quickly, accurately, and inexpensively [10]. This shifted the diagnostic criteria of T deficiency from purely clinical to laboratory dependent. Nonetheless, clinical use of T was rare in the 1980s and 1990s due to concern that high levels of either endogenous or exogenous T was directly related to the carcinogenesis of prostate cancer. In the early 2000s, a large-scale literature review strongly suggested there was not a causal relationship between T levels and prostate cancer, but there is ongoing controversy [10].

As the clinical use of T increased, there was growing concern that T might be related to cardiovascular (CV) events based on previous studies suggesting that men are at greater risk than women for CV disease [10]. There have been conflicting results among retrospective studies and meta-analyses have been complicated by inclusion of low-medium quality studies [11]. Additionally, none of the randomized controlled trials (RCT) published to date have been adequately powered to assess CV events [11]. The TRAVERSE trial, a large clinical trial of a transdermal testosterone gel versus a placebo gel, began in 2018 and is the first RCT adequately powered to assess CV events in men undergoing TT for 5 years [12]. The results of this RCT have the potential to change the standard of care, but may take up to a decade to be published. For now, the CV risks of TT remain inconclusive.

Testosterone therapy in cisgender men

Classical hypogonadism is a clinical syndrome defined by failure of adequate T production by the testis, classically attributed to either primary dysfunction of the testis (primary or hypergonadotropic hypogonadism) or to impaired central regulation of the testis (secondary or hypogonadotropic hypogonadism) [13]. Prior to initiating workup for identifying the source of hypogonadism, diagnosis of primary or secondary hypogonadism requires repeatedly substandard levels of serum T and clinical symptoms of T deficiency such as low sexual desire, reduced bone and muscle mass, erectile dysfunction, or gynecomastia [13]. The American Urological Association suggests a diagnosis of T deficiency after at least two early morning total T measurements below 300 ng/dL on separate occasions [14]. TT in these patients has well-defined clinical benefits and should be provided with the minimum dosing required to achieve serum T levels to the normal physiologic range of 450–600 ng/dL, which represents a viable range for all age-groups [3, 15].

Individual variation in the normal age-related decline of serum T has led to the identification of late-onset hypogonadism, a syndrome characterized by clinical and serological features of T deficiency in older men with no attributable cause besides age [16]. While late-onset hypogonadism is a well-established clinical entity, the role of TT in the absence of any identifiable pituitary, hypothalamic, or testicular disease is uncertain [17, 18]. In 2015 the U.S. Food and Drug Administration released a mandate stating that T preparations are approved only for men with hypogonadism due to identified causes [19]. However, the results of recent multicenter TT trials in older men indicate a significant improvement in sexual function, bone density, and anemia [20,21,22]. In support of this, a number of clinical practice guidelines from other expert groups argue that TT provides benefit to older men with late-onset hypogonadism and should be offered on an individual basis [23, 24].

Apart from these instances, there has been a substantial increase in TT among healthy, middle-aged cisgender males in the last decade [25]. Some have attributed this to inappropriate usage, likely due to the availability of more convenient T preparations or direct-to-consumer advertising encouraging use of T for vague symptoms such as decreased energy or sexual interest [26, 27]. Some cisgender gay and bisexual men may use T for its anabolic effects to increase muscularity, given the emphasis of bodily physique and sexual vigor in the gay community [28]. Others have classified this spike in usage as completely appropriate, likely due to increased screening of T in patients with erectile dysfunction or diabetes leading to increased diagnosis of T deficiency [29, 30]. Regardless, it should be emphasized that TT should only be prescribed to cisgender males in the setting of clinical symptoms of androgen deficiency and repeatedly substandard levels of serum. Although generally a safe therapy, TT is firmly associated with infertility, gynecomastia, acne, and erythrocytosis [3, 13]. As long-term safety data is lacking, issues related to prostate cancer, CV disease, and sleep apnea are not fully resolved and warrants continuous monitoring of patients on TT [30,31,32].

Testosterone therapy in cisgender women

While T has been historically categorized as a male hormone, there is growing interest in the role of T and other androgens in women’s health, particularly regarding sexual function. In addition to their role as a biosynthetic precursor to estrogen in women, androgens are also crucial for hormonal homeostasis and development of female reproductive tissues [33]. Further, androgens are known to influence bone remodeling, body fat and muscle composition, atherosclerosis, breast cell proliferation, cognition, and sexual desire [4]. While low levels of circulating androgens may theoretically have detrimental effects in any of these areas, it is important to note that accurate measurement of serum T in women is challenging and has not yet been proven a reliable predictor of clinical findings.

As opposed to the immediate decline of estrogen that follows menopause, serum T continuously decreases with age [34]. Despite conflicting evidence for low T as a cause of sexual dysfunction in women, TT in surgically or naturally menopausal cisgender women has shown to be a promising treatment [34]. Based on a number of RCTs and systematic reviews, TT in postmenopausal women with sexual dysfunction unresolved by estrogen therapy alone resulted in significant improvements in sexual function, sexual activity, and free serum T levels [35,36,37]. Outcomes related to safety are highly consistent in previous trials of T therapy in postmenopausal women both with and without simultaneous estrogen therapy, yet long-term safety is currently limited by observational trials only [38,39,40,41]. TT for cisgender women with sexual dysfunction remains an off-label use in most countries [42] However, several phase 3 clinical trials suggest transdermal T patches, dosed at 300 μg/day, with serial T measurements should be performed to ensure dosing is not exceeding physiologic levels [42]. Experts have also guided against the use of T that is formulated for men or dosed by a compounding pharmacy due to lack of safety data and worries about the ability to deliver an appropriate and consistent dose [43]. Unfortunately, since T preparations approved for women are highly limited, standard T preparations for men are often prescribed at 10 percent of male levels for use in women.

Cisgender females that identify as lesbian or bisexual may desire a mix of masculine and feminine characteristics, which requires highly individualized dosing targeted towards patient preferences. Various low dose configurations of T have been used transiently to obtain irreversible changes, such as deeper voice or facial hair growth [44]. Standardized dosing recommendations are not available for these patients due to considerable variation in therapeutic endpoints and baseline physiology between patients. Regardless, a trial of transdermal T, dosed at 1–2 mg/day, is recommended as a starting point, titrating to desired effect [44, 45]. Patients should be counselled on setting reasonable expectations based on the highly unpredictable timing and degree of changes with this form of TT [46]. As there is considerable overlap between goals for cisgender females and goals for genderqueer or transgender individuals, a more detailed discussion will be presented in the following section.

Testosterone therapy in LGBTQ populations

In addition to potential hypogonadism and sexual dysfunction described above, some members of LGBTQ populations experience GD and body uneasiness, which can be a significant source of physical, mental, and emotional distress that interferes with daily functioning [8]. TT is an important treatment in these patients as it has proven to be effective in improving body image and decreasing psychopathology associated with GD [47,48,49]. Although the exact number of LGBTQ persons on TT is not well documented, recent epidemiological studies suggest that the prevalence of a self-reported transgender identity ranges from 0.5 to 1.3% [50]. This estimate has nearly doubled from 10 years prior. In 2017, 1.8% of high school aged students identified as transgender or genderqueer, which is considerably higher than the general population [51]. It is important to note that not all members of LGBTQ populations will seek gender-affirming therapy (GAT). However, as the number of patients identifying as a member of LGBTQ populations increases, the number of individuals seeking TT is likely to increase as well.

When to start testosterone therapy in LGBTQ populations

For children and adolescents meeting the diagnostic criteria for GD, masculinizing treatment may involve a combination of gonadotropin-releasing hormone (GnRH) analogs and TT. GnRH analogs are preferred as initial GAT in this population since they reversibly suppress puberty and the development of secondary sex characteristics [52]. Because TT may produce irreversible phenotypic and physiologic changes, it is especially important to provide informed consent with a full disclosure of potential outcomes [52]. As proper informed consent requires the patient to have adequate decision making capacity, previous guidelines recommend against TT in patients less than 16 years old [52]. However, experts are now recommending that the decision to begin TT should be made on an individual basis despite limited literature on TT in patients less than 13 years old [52]. Additionally, all minors require parental or legal guardian consent to proceed with TT. The ideal timing of TT in this population remains unresolved.

Adults can provide consent for TT at any age as long as they have decision making capacity. The timing of TT-related changes is important to consider, as this may affect choice of GAT. For example, a retrospective study in 2017 by Beckwith et al. found that among transgender patients between 18 and 64 years of age, older age was associated with increased odds of a surgical approach, which may provide more immediate results [53]. However, for many patients surgical management is often not an option due to medical, financial, or social reasons and TT is the treatment of choice [54,55,56]. Although there is not a firm recommendation on when to begin TT therapy in adults, patients should have a therapeutic goal and must be assessed for medical contraindications prior to initiation of treatment.

Types of testosterone therapy and outcomes

Gender-affirming TT is offered in several preparations including intramuscular or subcutaneous injections, topical gels and creams, and transdermal patches with various dosing regimens (Table 1) [44]. Oral formulations are avoided due to extensive first pass metabolism and increased risk of hepatotoxicity [57]. Injections are the most commonly used preparation, as they do not require daily administration. Additionally, dosing of injections is more easily titratable to desired effects and are the least expensive preparation. Topical gels require application to the upper arms or shoulders daily, which must remain dry for at least 2 h after application. Further, extreme caution must be taken to avoid secondary exposure to others, especially women and children, due to safety concerns of gel-based T transference [58]. Transdermal patches are the most convenient to use, yet they are less commonly prescribed due to variable absorption, inconsistent physical effects, issues with titration, and cost.

Table 1 Recommended gender-affirming testosterone preparations and dosing.

Understanding the timing of physical changes after treatment initiation is crucial for guiding patient expectations related to TT. In general, lower doses are used for suppression of natal features and partial masculinization in lesbians and genderqueer patients [44]. Transgender men have lower basal levels of T than cisgender men. Therefore, transgender men who desire complete virilization are treated with higher doses of T to achieve a normal male physiologic range of total T between 450 and 600 ng/dL. Desirable physical effects such as deepening of the voice, fat redistribution, clitoral enlargement, cessation of menses, decreased body uneasiness, decreased GD, and increased libido can be observed as early as 3 months after beginning TT (Fig. 1) [7]. Significant results including increased muscle mass and facial/body hair growth can be observed within 6 months, and if desired, maximum virilization effects can be achieved within 3–5 years [59]. Adverse effects such as acne, male pattern baldness, and vaginal atrophy will likely develop within the first year of TT.

Fig. 1: Physical, physiologic, and mental status effects of TT.
figure 1

Recreated from ref. [7]. Wk week(s), Mo months(s), Y year(s).

The existing data on outcomes related to TT and GAHT in general are complex and difficult to interpret [60]. Many studies have shown high rates of satisfaction with rarely cited feelings of regret in patients who have received or are receiving TT [60]. A systematic review by Baker et al. noted improvement in quality of life and reduction in perceived stress, anxiety, and depression, among patients using TT [61]. However, the level of evidence for these conclusions is low due to study bias, small sample sizes, and confounding variables [61]. With careful patient selection and physician monitoring, TT is considered a safe treatment and has not been shown to be related to increased use of alcohol, drugs, aggression, negative mental health outcomes, or suicidality [7, 47, 62]. Despite these promising findings, additional high-quality studies are needed to gain a more nuanced understanding of effectiveness and limitations of TT.

Additional considerations for LGBTQ populations on or considering testosterone therapy

Medical contraindications, potential complications, and limitations of treatment should be discussed with patients prior to beginning treatment with TT. Importantly, TT is contraindicated in patients with active sex hormone-sensitive cancers. Those with a history of such cancers should consult an oncologist before proceeding [44]. Implications on fertility are discussed later in this review. In addition to previously mentioned acne and hair loss, additional side effects may include vaginal itchiness and dryness. For those with concerns of hair loss, 1 mg of oral finasteride has been advised, and over-the-counter lubricants may be used to address vaginal dryness [63, 64]. In women who have undergone an oophorectomy and have stopped or irregularly use TT, bone demineralization is a common complication [65,66,67]. Additionally, some studies have suggested CV, cerebrovascular, and oncological safety concerns including a theoretical link to prostate cancer in biological males [31]. However, long-term evidence is limited, and more research is needed in these areas in order to draw meaningful conclusions [68]. Limitations of treatment such as the inability of TT to change height and bone structure after puberty, or affect subcutaneous fat mass without the initiation or increase in physical activity, should also be communicated to patients [60].

While on TT it is important for patients to meet regularly with their provider. Total T, hemoglobin, and hematocrit should be monitored regularly during the first year on TT [14]. Current evidence does not support monitoring lipids, hemoglobin A1c, or fasting blood glucose unless there is a separate indication [13]. In complex cases, monitoring sex hormone binding globulin, albumin, and liver function tests can be decided at the clinician’s discretion [14]. Age appropriate breast and cervical cancer screening are strongly recommended for biological females. Additionally, screening for osteopenia and osteoporosis is recommended in those with pertinent risk factors [52]. In such cases, calcium and vitamin D supplementation may be offered.

Fertility preservation for LGBTQ populations on or considering testosterone therapy

Although it is clear that gender-affirming surgeries involving removal of reproductive organs are sterilizing, there is conflicting evidence on the effects of gender-affirming TT on fertility. Multiple studies by the World Health Organization (WHO) Task Force on Methods for the Regulation of Male Fertility showed reversible suppression of spermatogenesis after 6 months of intramuscular T injections [69,70,71]. However, the rates of azoospermia following T injections in each of these studies varied greatly, ranging from 64 to 98%. In addition to the inconsistent sterilizing effect of T in these studies, the reversibility of sterilization following TT in these studies may not be generalizable to individuals who have been on TT for longer durations. In a survey of transgender men who achieved pregnancy, 32% conceived while still on testosterone [72]. Interestingly, over half of participants in this study had been on TT for over 2 years and nearly 80% of those who discontinued T to conceive resumed menses within 6 months. As the reproductive consequences of TT are unclear and the process of stopping TT to conceive can be distressing for transitioning patients, current counseling guidelines are centered around initiation of fertility preservation prior to TT [73].

It is important to consider the challenges that people on or considering gender-affirming TT face in making reproductive choices and in gaining access to fertility preservation. Individuals who begin TT early in life are faced with making long-term decisions about fertility during periods when they may not yet have a partner or have not made plans about family building [73, 74]. Further, the cost of fertility preservation in addition to the cost of GAT for young individuals who may not yet be financially stable can be a significant barrier. Nonetheless, cryopreservation of oocytes or embryos for biological females and sperm banking for biological males with subsequent use in assisted reproductive technologies including in vitro fertilization are commonly used fertility preservation techniques in LGBTQ populations [75, 76]. Both processes require some method of harvest or collection procedure and a yearly fee for cryopreservation. Technological advances in oocyte vitrification techniques have greatly improved live birth rates from frozen oocytes, thus removing the need for fertilization of oocytes with partner or donor sperm prior to freezing [75, 76]. Similarly, technological advances in sperm collection and banking have resulted in successful fertilization and births using sperm up to 20 years old.

Misuse of testosterone therapy among LGBTQ populations

The illegitimate use of anabolic steroids and over-prescription of testosterone medications are well-covered topics in the media and literature [77]. Very little, however, has been published surrounding the misuse or misguided administration of TT in LGBTQ populations. As TT has the potential for harm if used inappropriately, it is important to understand the scope of misuse and mechanisms that enable this activity. With various legitimate and illegitimate methods to acquire TT, it is imperative that proper education and safety regulations are established.

The use of self-administered GAHT including TT is an important yet understudied area in the literature. As such, the true prevalence is not well understood. In 2000, a survey of 263 transgender participants in Washington, DC, found that of the 52% of participants that had used GAHT at some point in their lives [78]. Only 34% received physician surveillance of blood levels during this time. Furthermore, 58% of the participants who had used GAHT did so through non-prescribed methods, acquiring them from acquaintances or illegitimate sellers [78]. A study published in the American Journal of Public Health in 2013 found that 43% of the 433 participants had used hormonal therapy in the past, and a quarter of these participants had used non-prescribed hormonal therapy [79]. These results were consistent with a 2014 study from the United Kingdom examining transgender participants attending gender reassignment clinics. Of the 23% of participants who had used GAHT, 70% acquired their medication online [80]. Those who purchased hormones online were also reported to be less informed about the various risks and side effects of the treatment [80]. A 2020 study using data from the US Transgender Survey found that of the 12,307 individuals using hormones, nearly 10% did not have a prescription [80]. Potential explanations for the increase in back channel use include barriers to access such as discrimination in health care, lack of health insurance coverage, and cost as well as inadequate health policy and regulations for prescribers [80, 81].

Regardless of the motivating factors, purchasing and using TT without proper knowledge or guidance opens the door to various health risks, which could otherwise be avoided. With numerous options for the acquisition of TT, proper education and safety measures must be in place. Law enforcement bodies must work to close channels that sell unregulated and fraudulent T preparations, and firm guidelines and penalties should be explored for providers that inappropriately perpetuate misuse of TT.

Conclusion

TT is a major GAT in LGBTQ populations with a spectrum of physical and physiologic effects. Cisgender gay and bisexual men may be treated with TT for hypogonadism or sexual dysfunction. Cisgender lesbian and bisexual women may pursue TT for postmenopausal sexual dysfunction, suppression of natal features, or partial masculinization. Transgender men and genderqueer patients may desire TT to present as masculine. Ideal timing for initiation of TT remains unresolved and an individualized approach is recommended after considering symptoms, goals, and health history. Patients must be extensively counseled prior to beginning TT as it can cause potentially irreversible infertility. Finally, illegitimate acquisition and misuse of TT has increased in recent years, and judicious prescribing and close physician monitoring can help to ensure safe and effective treatment.

References

  1. 1.

    Nieschlag E, Nieschlag S. Endocrine history: the history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180:R201–12.

    CAS  PubMed  Google Scholar 

  2. 2.

    Rastrelli G, Corona G, Maggi M. Testosterone and sexual function in men. Maturitas. 2018;112:46–52.

    CAS  PubMed  Google Scholar 

  3. 3.

    Tsametis CP, Isidori AM. Testosterone replacement therapy: for whom, when and how? Metabolism. 2018;86:69–78.

    CAS  PubMed  Google Scholar 

  4. 4.

    Vegunta S, Kling JM, Kapoor E. Androgen therapy in women. J Women’s Health. 2019;29:57–64.

    Google Scholar 

  5. 5.

    Radix A. Hormone therapy for transgender adults. Urol Clin North Am. 2019;46:467–73.

    PubMed  Google Scholar 

  6. 6.

    American Psychological Association. Guidelines for psychological practice with transgender and gender nonconforming people. Am Psychol. 2015;70:832–64.

    Google Scholar 

  7. 7.

    Defreyne J, T’Sjoen G. Transmasculine hormone therapy. Endocrinol Metab Clin North Am. 2019;48:357–75.

    PubMed  Google Scholar 

  8. 8.

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DMS-5®). Washington, DC. American Psychiatric Pub; 2013.

  9. 9.

    Nieschlag E, Nieschlag S. Testosterone deficiency: a historical perspective. Asian J Androl. 2014;16:161.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Morgentaler A, Traish A. The history of testosterone and the evolution of its therapeutic potential. Sex Med Rev. 2020;8:286–96.

    PubMed  Google Scholar 

  11. 11.

    Gagliano-Jucá T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nat Rev Cardiol. 2019;16:555–74.

    PubMed  Google Scholar 

  12. 12.

    Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study. 2022. NCT03518034. https://www.clinicaltrials.gov/ct2/show/NCT03518034. Accessed 21 Sept 2021.

  13. 13.

    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2010;95:2536–59.

    CAS  PubMed  Google Scholar 

  14. 14.

    Mulhall JP, Trost LW, Brannigan RE, Kurtz EG, Redmon JB, Chiles KA, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423.

    PubMed  Google Scholar 

  15. 15.

    Bhasin S, Enzlin P, Coviello A, Basson R. Sexual dysfunction in men and women with endocrine disorders. Lancet. 2007;369:597–611.

    CAS  PubMed  Google Scholar 

  16. 16.

    Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Eur J Endocrinol. 2008;159:507–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S. Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol. 2013;9:414–24.

    CAS  PubMed  Google Scholar 

  18. 18.

    Cunningham GR. Testosterone replacement therapy for late-onset hypogonadism. Nat Rev Urol. 2006;3:260–7.

    CAS  Google Scholar 

  19. 19.

    FDA Drug Safety Communication. FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. FDA. 2018. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-cautions-about-using-testosterone-products-low-testosterone-due. Accessed 13 June 2021.

  20. 20.

    Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. N. Engl J Med. 2016;374:611–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Bhasin S, Matsumoto AM, et al. Testosterone treatment and sexual function in older men with low testosterone levels. J Clin Endocrinol Metab. 2016;101:3096–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med. 2017;177:480.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Dimopoulou C, Ceausu I, Depypere H, Lambrinoudaki I, Mueck A, Pérez-López FR, et al. EMAS position statement: testosterone replacement therapy in the aging male‏. Maturitas. 2016;84:94–99.

    CAS  PubMed  Google Scholar 

  24. 24.

    Isidori AM, Balercia G, Calogero AE, Corona G, Ferlin A, Francavilla S, et al. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Investig. 2015;38:103–12.

    CAS  Google Scholar 

  25. 25.

    Layton JB, Li D, Meier CR, Sharpless JL, Stürmer T, Jick SS, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. J Endocrinol Metab. 2014;99:835–42.

    CAS  Google Scholar 

  26. 26.

    Handelsman DJ. Global trends in testosterone prescribing, 2000–2011: expanding the spectrum of prescription drug misuse. Med J Aust. 2013;199:548–51.

    PubMed  Google Scholar 

  27. 27.

    Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013;173:1465.

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Purcell DW, Wolitski RJ, Hoff CC, Parsons JT, Woods WJ, Halkitis PN. Predictors of the use of viagra, testosterone, and antidepressants among HIV-seropositive gay and bisexual men. AIDS. 2005;19:S57–S66.

    CAS  PubMed  Google Scholar 

  29. 29.

    Hackett G, Kirby M, Wylie K, Heald A, Ossei-Gerning N, Edwards D, et al. British society for sexual medicine guidelines on the management of erectile dysfunction in men—2017. J Sex Med. 2018;15:430–57.

    PubMed  Google Scholar 

  30. 30.

    Hackett GI, Cole NS, Deshpande AA, Popple MD, Kennedy D, Wilkinson P. Biochemical hypogonadism in men with type 2 diabetes in primary care practice. Br J Diabetes Vasc. 2009;9:226–31.

    CAS  Google Scholar 

  31. 31.

    Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17:132–43.

    CAS  PubMed  Google Scholar 

  32. 32.

    Hackett GI. Testosterone replacement therapy and mortality in older men. Drug Saf. 2016;39:117–30.

    CAS  PubMed  Google Scholar 

  33. 33.

    Hodgson TK, Braunstein GD Physiological Effects of Androgens in Women. In: Azziz R, Nestler JE, Dewailly D (eds). Androgen Excess Disorders in Women. 2nd ed. Totowa, NJ: Humana Press; 2007. p. 49–62.

  34. 34.

    Elraiyah T, Sonbol MB, Wang Z, Khairalseed T, Asi N, Undavalli C, et al. The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99:3536–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, et al. Testosterone for low libido in postmenopausal women not taking estrogen. N. Engl J Med. 2008;359:2005–17.

    CAS  PubMed  Google Scholar 

  36. 36.

    Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:1582–9.

    CAS  PubMed  Google Scholar 

  37. 37.

    Somboonporn W, Bell RJ, Davis SR. Testosterone for peri and postmenopausal women. Cochrane Database Syst Rev. 2005;4:CD004509.

    Google Scholar 

  38. 38.

    Panzer C, Guay A. Testosterone replacement therapy in naturally and surgically menopausal women. J Sex Med. 2009;6:8–18.

    CAS  PubMed  Google Scholar 

  39. 39.

    Davis SR, Braunstein GD. Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med. 2012;9:1134–48.

    CAS  PubMed  Google Scholar 

  40. 40.

    Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause. 2004;11:531–5.

    PubMed  Google Scholar 

  41. 41.

    Nachtigall L, Casson P, Lucas J, Schofield V, Melson C, Simon JA. Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen. Gynecol Endocrinol. 2011;27:39–48.

    CAS  PubMed  Google Scholar 

  42. 42.

    Clayton AH, Goldstein I, Kim NN, Althof SE, Faubion SS, Faught BM, et al. The International Society for the Study of Women’s Sexual Health Process of Care for Management of Hypoactive Sexual Desire Disorder in Women. Mayo Clin Proc. 2018;93:467–87.

    PubMed  Google Scholar 

  43. 43.

    Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH, et al. Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99:3489–510.

    CAS  PubMed  Google Scholar 

  44. 44.

    UCSF Transgender Care, Department of Family and Community Medicine, University of California San Francisco. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People. Deutsch MB (ed). 2nd ed. June 2016. transcare.ucsf.edu/guidelines.

  45. 45.

    Cocchetti C, Ristori J, Romani A, Maggi M, Fisher AD. Hormonal treatment strategies tailored to non-binary transgender individuals. J Clin Med. 2020;9:1609.

    CAS  PubMed Central  Google Scholar 

  46. 46.

    Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. Int J Transgend. 2012;13:165–232.

    Google Scholar 

  47. 47.

    Heylens G, Verroken C, Cock SD, T’Sjoen G, Cuypere GD. Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder. J Sex Med. 2014;11:119–26.

    PubMed  Google Scholar 

  48. 48.

    Fisher AD, Castellini G, Ristori J, Casale H, Cassioli E, Sensi C, et al. Cross-sex hormone treatment and psychobiological changes in transsexual persons: two-year follow-up data. J Clin Endocrinol Metab. 2016;101:4260–9.

    CAS  PubMed  Google Scholar 

  49. 49.

    Fisher AD, Castellini G, Bandini E, Casale H, Fanni E, Benni L, et al. Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria. J Sex Med. 2014;11:709–19.

    CAS  PubMed  Google Scholar 

  50. 50.

    Zucker KJ. Epidemiology of gender dysphoria and transgender identity. Sex Health. 2017;14:404–11.

    PubMed  Google Scholar 

  51. 51.

    Johns MM, Lowry R, Andrzejewski J, Barrios LC, Demissie Z, McManus T, et al. Transgender Identity and Experiences of Violence Victimization, Substance Use, Suicide Risk, and Sexual Risk Behaviors Among High School Students—19 States and Large Urban School Districts, 2017. MMWR Morb Mortal Wkly Rep. 2019;68:67–71.

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:3869–903.

    PubMed  Google Scholar 

  53. 53.

    Beckwith N, Reisner SL, Zaslow S, Mayer KH, Keuroghlian AS. Factors associated with gender-affirming surgery and age of hormone therapy initiation among transgender adults. Transgend Health. 2017;2:156–64.

    PubMed  PubMed Central  Google Scholar 

  54. 54.

    James SE, Herman JL, Rankin S, Keisling M, Mottet L, Anafi M. The Report of the 2015 U.S. Transgender Survey. National Center for Transgender Equality. 2016. https://transequality.org/sites/default/files/docs/usts/USTS-Full-Report-Dec17.pdf. Accessed 19 June 2021.

  55. 55.

    Moravek MB. Gender-affirming hormone therapy for transgender men. Clin Obstet Gynecol. 2018;61:687–704.

    PubMed  Google Scholar 

  56. 56.

    Fabris B, Bernardi S, Trombetta C. Cross-sex hormone therapy for gender dysphoria. J Endocrinol Investig. 2015;38:269–82.

    CAS  Google Scholar 

  57. 57.

    Irving A, Lehault WB. Clinical pearls of gender-affirming hormone therapy in transgender patients. Ment Health Clin. 2017;7:164–7.

    PubMed  Google Scholar 

  58. 58.

    Miller MG, Rogol AD, ZumBrunnen TL. Secondary exposure to testosterone from patients receiving replacement therapy with transdermal testosterone gels. Curr Med Res Opin. 2012;28:267–9.

    CAS  PubMed  Google Scholar 

  59. 59.

    Costa LB, Rosa-e-Silva A, Medeiros S, Nacul A, Carvalho B, Benetti-Pinto C, et al. Recommendations for the use of testosterone in male transgender. Rev Bras Ginecol Obstet. 2018;40:275–80.

    PubMed  Google Scholar 

  60. 60.

    T’Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of transgender medicine. Endocr Rev. 2019;40:97–117.

    PubMed  Google Scholar 

  61. 61.

    Baker KE, Wilson LM, Sharma R, Dukhanin V, McArthur K, Robinson KA. Hormone therapy, mental health, and quality of life among transgender people: a systematic review. J Endocr Soc. 2021;5:bvab011.

    PubMed  PubMed Central  Google Scholar 

  62. 62.

    Colton Meier SL, Fitzgerald KM, Pardo ST, Babcock J. The Effects of Hormonal Gender Affirmation Treatment on Mental Health in Female-to-Male Transsexuals. J Gay Lesbian. J Gay Lesbian Ment Health. 2011;15:281–99.

    Google Scholar 

  63. 63.

    Moreno-Arrones OM, Becerra A, Vano-Galvan S. Therapeutic experience with oral finasteride for androgenetic alopecia in female-to-male transgender patients. Clin Exp Dermatol. 2017;42:743–8.

    CAS  PubMed  Google Scholar 

  64. 64.

    Leiblum S, Bachmann G, Kemmann E, Colburn D, Swartzman L. Vaginal atrophy in the postmenopausal woman: the importance of sexual activity and hormones. JAMA. 1983;249:2195–8.

    CAS  PubMed  Google Scholar 

  65. 65.

    Miyajima T, Kim YT, Oda H. A study of changes in bone metabolism in cases of gender identity disorder. J Bone Min Metab. 2012;30:468–73.

    CAS  Google Scholar 

  66. 66.

    Goh HH, Ratnam SS. Effects of hormone deficiency, androgen therapy and calcium supplementation on bone mineral density in female transsexuals. Maturitas. 1997;26:45–52.

    CAS  PubMed  Google Scholar 

  67. 67.

    Kesteren PV, Lips P, Gooren LJG, Asscheman H, Megens J. Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol. 1998;48:347–54.

    Google Scholar 

  68. 68.

    Connelly PJ, Marie Freel E, Perry C, Ewan J, Touyz RM, Currie G, et al. Gender-affirming hormone therapy, vascular health and cardiovascular disease in transgender adults. Hypertension. 2019;74:1266–74.

    CAS  PubMed  Google Scholar 

  69. 69.

    Walker WH. Non-classical actions of testosterone and spermatogenesis. Philos Trans R Soc Lond B Biol Sci. 2010;365:1557–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30:2–13.

    CAS  PubMed  Google Scholar 

  71. 71.

    Gu Y, Liang X, Wu W, Liu M, Song S, Cheng L, et al. Multicenter contraceptive efficacy trial of injectable testosterone undecanoate in Chinese men. J Clin Endocrinol Metab. 2009;94:1910–5.

    CAS  PubMed  Google Scholar 

  72. 72.

    Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124:1120–7.

    CAS  PubMed  Google Scholar 

  73. 73.

    Moravek MB. Fertility preservation options for transgender and gender-nonconforming individuals. Curr Opin Obstet Gynecol. 2019;31:170–6.

    PubMed  Google Scholar 

  74. 74.

    Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019;112:1022–33.

  75. 75.

    Cobo A, Bellver J, Domingo J, Pérez S, Crespo J, Pellicer A, et al. New options in assisted reproduction technology: the Cryotop method of oocyte vitrification. Repro Biomed Online. 2008;17:68–72.

    Google Scholar 

  76. 76.

    Mitu K. Transgender reproductive choice and fertility preservation. AMA J Ethics. 2016:18:1119–25.

    PubMed  Google Scholar 

  77. 77.

    Jasuja GK, Bhasin S, Rose AJ. Patterns of testosterone prescription overuse. Curr Opin Endocrinol Diabetes Obes. 2017;24:240–5.

    PubMed  Google Scholar 

  78. 78.

    Xavier JM. The Washington, DC Transgender Needs Assessment Survey. Administration for HIV/Aids of the District of Columbia Government. 2000. http://www.glaa.org/archive/2000/tgneedsassessment1112.shtml. Accessed 13 June 2021.

  79. 79.

    Rotondi NK, Bauer GR, Scanlon K, Kaay M, Travers R, Travers A. Nonprescribed Hormone Use and Self-Performed Surgeries: “Do-It-Yourself” Transitions in Transgender Communities in Ontario, Canada. Am J Public Health. 2013;103:1830–6.

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Mepham N, Bouman WP, Arcelus J, Hayter M, Wylie KR. People with Gender Dysphoria Who Self‐Prescribe Cross‐Sex Hormones: Prevalence, Sources, and Side Effects Knowledge. J Sex Med. 2014;11:2995–3001.

    PubMed  Google Scholar 

  81. 81.

    Stroumsa D, Crissman HP, Dalton VK, Kolenic G, Richardson CR. Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey. Ann Fam Med. 2020;18:528–34.

    PubMed  PubMed Central  Google Scholar 

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ANT and ECO conceived and designed the manuscript. ANT, AVS, and VRP collected data, interpreted findings, and drafted the manuscript with support from ECO. All authors participated in critical revision and agreed on final approval of the manuscript.

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Tijerina, A.N., Srivastava, A.V., Patel, V.R. et al. Current use of testosterone therapy in LGBTQ populations. Int J Impot Res (2021). https://doi.org/10.1038/s41443-021-00490-z

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