Hormone Replacement Therapy (HRT) indicates a hormonal therapy in which the individual takes hormones either to supplement a lack of hormone production or adjust hormone levels and/or gendered hormonal categories. HRT is generally understood to refer to treatment with steroid “sex” hormones, that is, estrogen, progesterone,and androgen (generically referred to as testosterone). These therapies are used to treat a medically defined issue or modify aspects of the body related to gender. Both synthetic and/or naturally occurring (plant or animal sources) may be used, yet HRT usually refers to synthetic hormone use.

The most common uses of HRT include menopause; andropause; transgender individuals; for individuals diagnosed with an intersex/DSD (Disorder/Divergence of Sex Development) syndrome; and for non–DSD, non-transgender gendered somatic (physical and/or aesthetic) aspects (facial hair, breast growth, etc). Hormonal birth control (the contraceptive pill) and other therapies that regulate the reproductive system (such as fertility therapy), the use of androgens to treat depression, and the use of anabolic steroids for bodybuilding, are not commonly included in this category.

Sex steroids/sex hormones and gender

All of the above-mentioned HRTs were historically developed in the context of a combination of biochemical research regarding the development of the gendered body, reproductive cycles, and sexual behaviour, as well as the social conception of sexual behaviour, gender roles, and gendered somatic traits. HRTs usually match hormonal and social gender categories (independently of how their biological sex is defined); however, there are exceptions (e.g., in hormonal use not commonly considered in the HRT category, such as for bodybuilding, the treatment of depression).

The terms sex steroids, gonadal steroids, and sex hormones are usually used synonymously. Sex hormones are produced in the body by the gonads (ovaries and testes), the adrenal glands, or through the conversion from one category of hormone (found in tissues such as fat) to another.

The terms sex steroids, gonadal steroids, and sex hormones are usually used synonymously. Sex hormones are produced in the body by the gonads (ovaries and testes), the adrenal glands, or through the conversion from one category of hormone (found in tissues such as fat) to another. Their chemical makeup was understood and synthesised at the beginning of the 1920s. However, their effects on the reproductive system and the somatic aspects of the gendered body were explored through experiments with the gonads from the beginning of the 1800s (Crocetti 2013b).

The role of the sex hormones in the reproductive cycle and the development of gendered somatic traits lead them to be categorised into gendered categories (estrogens and progesterones—female; androgens—male). All three primary categories of hormones are present in all bodies at different levels and also play a role in non-reproductive health.

Literature in the medical and social sciences may attribute complex gendered social behaviours (such as gendered behaviour, gender identity, or sexual orientation) to hormonal levels, or even HRT, yet the experimental evidence is scarce. Often this literature fails to make a clear separation between the distinct categories of chromosomal sex (genotype), gonadal sex (and other gendered biological categories), somatic gender (phenotype), gender stereotypes, gender identity, stereotyped gendered behaviour, gender presentation, cognitive ability, sexual object choice, and sexual orientation

Literature in the medical and social sciences may attribute complex gendered social behaviours (such as gendered behaviour, gender identity, or sexual orientation) to hormonal levels, or even HRT, yet the experimental evidence is scarce. Often this literature fails to make a clear separation between the distinct categories of chromosomal sex (genotype), gonadal sex (and other gendered biological categories), somatic gender (phenotype), gender stereotypes, gender identity, stereotyped gendered behaviour, gender presentation, cognitive ability, sexual object choice, and sexual orientation. This confusion of categories is often correlated to the gendered brain model that states that prenatal hormonal imprinting shapes these complex social behaviours. The high percentage of human variation regarding these aspects indicates the need for a more complex model.

Sex hormones have been shown to have a direct role in the reproductive process, the shaping of gendered somatic traits, mood and energy level, as well as many non-gendered health aspects such as cardiac health, bone density, and tissue repair. They do not directly affect adult sexual orientation or gender identity. Increased experimental evidence regarding HRT has led to concern that the non-gendered health effects of sex hormones are understudied.

HRT for individuals medicalised for
an Intersex/DSD syndrome

HRT for Klinefelter’s Syndrome (XXY) has the duel aim of masculinising physical and social characteristics. Androgen HRT reduces the fat to muscle ratio, and increases body hair, thereby increasing male somatic traits, it also increases libido and energy levels that are socially perceived as masculine. KS patient activists have questioned the necessity of HRT for their syndrome, seeing as it does not affect functional symptoms, such as sterility and cognitive variation. They indicate HRT mainly functions to medicalise the perception of KS patients as feminine and homosexual.

HRT is used differently for Intersex/DSD based on the specific syndrome category and how the person has been medicalised. HRT is used in: Klinefelter’s syndrome (three sex chromosomes: XXY); in cases where a gonadectomy has been performed (particularly for Androgen Insensitivity Syndrome—AIS—and gonadal dysgenesis, the presence of incomplete or mixed gonadal tissue); in cases where the gonad has not formed; or where there is low hormone production as in Turners syndrome (one sex chromosome: O, X). HRT for Klinefelter’s syndrome (KS) has the dual aim of masculinising physical and social characteristics. Androgen HRT reduces the fat-to-muscle ratio and increases body hair, thereby increasing male somatic traits. Androgen HRT also increases libido and energy levels that are socially perceived as masculine. KS patient activists have questioned the necessity of HRT for their syndrome, seeing as it does not affect functional symptoms, such as sterility and cognitive variation (present in rarer forms). Activists indicate that HRT mainly functions to medicalise the perception of KS patients as feminine and homosexual. However, many patients enjoy both the physical and energetic aspects of HRT. KS patient activists indicate there is a need for more research regarding long-term health effects and sterility.

Gonadectomy necessitates HRT, as hormones are important for many aspects of total body health. Gonadectomies performed in early childhood, or before the age of consent, are one of the controversial bioethical components of DSD medical care. While there is experimental evidence that mixed gonadal tissue indicates a high cancer risk, there is no data that this is the case for other DSDs, such as AIS (androgen insensitivity syndrome) (Crocetti 2013a). In AIS, gonadectomies are performed for psychosocial reasons, to ensure a stable female gender identity in a person that is somatically female and has XY sex chromosomes. In the days before full diagnosis disclosure, the patient would be informed (at best) they had had a cancer risk leading to additional anxiety. While some AIS patients do autonomously choose gonadectomy, they, too, indicate that until an actual health risk is established, this type of operation needs to be an individual choice. AIS HRT is generally not syndrome specific, given in the form of commercial birth control (the pill) that contains both estrogen and progesterone. Finding the right dose within the standardized commercial range can be very difficult. In addition, there is speculation that androgen therapy, or mixed androgen-estrogen therapy, might produce better health effects. However, institutionally, cross-gender HRT (i.e., an HRT that does not correspond to the social gender category regardless of the chromosomal gender) is made difficult.

Androgen Insensitivity Syndrome (AIS) HRT is generally not syndrome specific, given in the form of commercial birth control (the pill) that contains both estrogen and progesterone. Finding the right dose within the standardised commercial range can be very difficult. In addition, there is speculation that androgen therapy, or a mixed androgen-estrogen therapy might produce better health effects. However, institutionally, cross-gender HRT (i.e., a HRT that does not correspond to the social gender category regardless of the chromosomal gender) is made difficult.

Topical androgen HRT may be used on the genitals for the 5-alpha reductase genetic diagnosis to increase the genital size and indicate if the body is receptive to androgens.

Congenital Adrenal Hyperplasia (CAH) can require HRT at puberty but primarily involves the use of glucocorticoids to reduce androgen levels produced by the adrenal glands.

Other HRTs for other DSD syndromes, like that of Turner’s syndrome, involve gender identity-specific HRT aimed at augmenting hormonal levels to a statistical norm.

HRT for menopause and andropause

The use of HRT for menopause is much more frequent than HRT for andropause. HRT may be used for pathological, age, and surgically
induced (removal of the gonads) menopause and andropause. Androgen Replacement Therapy (ART) is used to treat hypogonadism (low androgen
production) and the perceived effects of male ageing (andropause). The correlated symptoms range from fewer erections, reduced libido,
fatigue, depression, thinning skin, declining muscle mass and strength, and more body fat. ART side effects may include increased risks of acne, cardiac problems, liver disease, prostate cancer, and infertility. Historians indicate the use of male gonads throughout the 1800s as an elixir of life, energy enhancer, and potential cure for homosexuality, after which these uses fell into disrepute.

The term menopause derives from the Greek word pausis (cessation) and the root men (month), indicating the end of monthly cycles and the female reproductive phase. While noted through the cessation of the menstrual flow, menopause indicates the cessation of certain ovary (female gonad) functions, such as the release of ova (eggs) and the production of the estrogens and progestogens involved in the reproductive cycle.

HRT for menopause can include both estrogens and progestogens for individuals with an intact uterus or estrogen alone for those who have had a hysterectomy (removal of the uterus). HRT was indicated to treat the initial symptoms of menopause, such as hot flashes and mood swings. As research continued, HRT was also correlated to the treatment of vaginal dryness, osteoporosis (bone density loss), heart disease, depression, sleep quality, memory loss, joint pain, skin elasticity, and the general effects of ageing.

Following the discovery of high levels of estrogens in equine urine (present in both male and pregnant female horses), conjugated equine estrogens became the most common source of commercial estrogens. A popular alternative to conventional HRT is a synthetic hormone derived from the Mexican yam.

Since 2002, however, HRT for menopause has become controversial. The U.S. Women’s Health Initiative (WHI), and later the U.K. Million Women Study, released experimental results that HRT treatment coincides with an increased incidence of breast cancer, heart attacks, and strokes (Writing Group for the Women’s Health Initiative Investigators 2002). The study also found statistically significant decreases in rates of hip fracture and colorectal cancer. The WHI trial was scheduled to end in 2005; however, the combination-therapy part of the study was suspended in 2002 because the breast cancer risks associated with combination HRT seemed to outweigh the benefits. Figures indicated a drastic decrease in breast cancer rates after the mass suspension of HRT in 2002–2004 in the United States, results which, however, were not corroborated in Canada. Continued research indicates multiple factors in the risks and benefits of HRT, such as timing (immediately after menopause/ surgery or years after), estrogen-only versus estrogen and progestogen HRT, family disease history, doses, and types of hormones.

HRT for transgender individuals

HRT for transgender individuals adjusts the balance of sex hormones in the body, with the primary aim of shifting the gendered somatic traits (the secondary sex characteristics) towards that of ones gender identity.

HRT will not reverse somatic changes produced at puberty, leading to the argument for both early therapy and/or the hormonal delay of puberty. As indicated earlier, HRT is generally gender identity specific. Transgender HRT is referred to as male-to-female (MTF) or female-to-male (FTM), as it helps shift somatic traits from that of the gender assigned at birth (and chromosomal sex in the absence of an intersex condition) to that of the individual’s gender identity.

Estrogen HRT is used for breast growth and the redistribution of body fat and is therefore associated with the primary female somatic traits. Transgender HRT estrogen levels are often higher than replacement doses for cis-gender (having the same gendered identity as assigned at birth)women, although the official guideline for endocrinologists recommends maintaining sex hormone levels within the normal range for the person’s gender identity. Before institutional protocols were formed, many transgender women self-medicated with fluctuating doses based on availability. Doses are often reduced after gonadectomy (when performed) or in combination with anti-androgens (androgen-blocking agents). The most significant risk is the pro-thrombotic effect of estrogens (increased blood clotting). Increased dosages increase health risks (estrogen-sensitive cancer, heart disease, liver disease, heart disease, stroke, gallbladder disease, etc).

Progesterone is associated with fat distribution, skin elasticity, bone health, increased libido, increased energy, and increased sleep quality.
They are also associated with increased breast cancer risk in trans- and cis-gender individuals.

The half-life of testosterone in the blood is about 70 minutes, so a continuous supply of the hormone is necessary for somatic masculinization Testosterone HRT includes many forms of application: injection, transdermal (patches, creams, and gels), subcutaneous pellets, oral, and sublingual (buccal).

Anti-androgens block the binding of androgens to receptors in the body instead of blocking the production of androgens. Anti-androgens may be used to encourage breast growth and may slightly reduce body hair. Anti-androgens will also reduce the size of the gonads, prostate, and bladder. There are many different chemical versions of anti-androgens with varied respective side effects (including reduced libido, cardiac, and liver disease risk).

The half-life of testosterone in the blood is about 70 minutes, so a continuous supply of the hormone is necessary for somatic masculinization Testosterone HRT includes many forms of application: injection, transdermal (patches, creams, and gels), subcutaneous pellets, oral, and sublingual (buccal). Side effects of the hormone are accompanied by side effects from the form of use. Androgen HRT cause some irreversible effects in the body, such as the deepening of the voice, increase of body and facial hair, occasional baldness, and the enlargement of the clitoris. Reversible effects instead are increased libido, redistribution of body fat, cessation of ovulation and menstruation, increased muscle development (especially upper body), increased sweat and changes in body odour, acne (especially in the first few years of therapy), and increased red blood cell count. Androgen therapy has been clinically less frequent than estrogen and progestogen therapy, and medically supervised FTM HRT has a shorter clinical history than MTF HRT; therefore, the health risks are still under study. In particular cardiac health risks are to be correlated to other risk factors such as smoking and fat distribution. With long-term androgen therapy, ovaries may develop polycystic ovary syndrome that carries a risk of endometrial cancer. However, there is no significant data regarding the increase of FTM HRT-associated endometrial and ovarian cancer risk. There is a risk of liver damage and liver cancer with all testosterone formulations, but this is minimal in all forms except oral or where very high levels are administered.

HRT is part of the medical paradigm for legal gender change in most nations, often the second stage after the initial psychological counselling. In addition, many nations require sterilisation or gonadectomy for legal gender change. In the case of gonadectomy, HRT is necessary to avoid osteoporosis as well as many other health risks.

HRT for non-DSD, non-Transgender gendered somatic aspects

Cis-gender individuals (and their parents in the case of children) are also subject to social pressure and insecurity regarding their gender presentation. While not part of standardised medical protocol, individuals may use HRT to increase their gendered presentation.

HRT has been suggested for female children regarding somatic aspects such as body hair and muscle mass. In female adults, progesterone has been used to attempt to increase breast growth. Testosterone, however, is used by all genders to increase muscle mass.

About the Author

Daniela Crocetti is a Senior Research Fellow at the University of Huddersfield. Daniela has researched and published on Intersex medicalisation, the social history of gendered components of the body (such as hormones), and health activism.