Shri Swami Samarth institute of pharmacy
Many transgender individuals seek hormone therapy as part of their gender transition process . In transgender men , exogeneous testosterone is administered to induce virilization and suppress feminizing traits , while in transgender women , exogeneous estrogen is used to promote feminization , with anti-androgens helping to suppress masculinizing effects . This review examines prospective studies on the impact of hormone therapy on psychological functioning and quality of life in transgender people assessing changes over time with continued hormone Therapy . Gender dysphoria the clinical term for the experience of discomfort or distress due to a mismatch between one’s gender identify and assigned sex at birth. is commonly diagnosed in transgender individuals seeking such therapies . we sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people , eligible studies were those that assessed psychological outcomes such as mental health quality of life , and well -being in transgender individuals receiving gender-affirming hormone therapy.
Transgender individuals experience discord between their self-identified gender and biological sex. Raised in a gender different from their assigned sex at birth . some of these studies have shown , that these children often identify with the gender they were raised in , suggesting a possible biological basis for gender identify that is independent of societal or cultural influences . additionally , research on brain structure and function , as well as genetic studies , has indicated differences in the brains of transgender individuals compared to cisgender individuals , further supporting the idea that gender identify may have a neurobiological component . For instance , studies have found that certain areas of the brain in transgender individuals resembles those typically associated with their gender identify rather than their biological sex. Hormonal influences during prenatal development , as well as genetic factors , may also play a role in shaping gender identify. However , the exact mechanisms behind transgender identify remain unclear , and it is likely that a combination of genetic , hormonal , environmental , and social factors contribute to an individual’s sense of gender . It’s important to note that while research is ongoing, the current understanding of transgender experiences emphasizes the complexity and diversity of human gender identity. The experience of being transgender is multifaceted and cannot be fully explained by any single factor, biological or otherwise. The 20th century saw significant advancements in understanding gender identity, and Magnus Hirschfeld, a German physician and sexologist, was a key figure in this development. In 1923, Hirschfeld used the term "transsexual" to describe individuals who desired to live according to their experienced gender, rather than the gender assigned to them at birth. This concept was groundbreaking at the time, as it helped to distinguish between sexual orientation, gender identity, and biological sex. Hirschfeld's work laid the foundation for modern discussions about gender and sexuality, though his ideas were initially met with resistance and often marginalized. His pioneering efforts contributed to the early recognition of transgender experiences, and his research was part of broader movements in the early 20th century that sought to challenge traditional views on gender and sexual norms. Despite the progress in the early 20th century, it wasn't until much later that trans identities and issues gained wider recognition and acceptance, especially with the rise of transgender advocacy in the latter part of the century. Hirschfeld's legacy, however, remains influential in contemporary conversations about gender diversity.
1 .Gender Dysphoria : The core characteristic of gender dysphoria is the significant distress stemming from the incongruence between an individual's experienced gender identity and their biological sex. Transgender individuals often experience this discord, which can lead them to seek medical interventions, such as hormone therapy, to align their physical appearance with their gender identity.
2. Hormone Therapy: The number of transgender individuals seeking cross-sex hormone therapy has increased over time. Administering exogenous hormones (like testosterone for trans men or estrogen for trans women) is medically necessary for many individuals to help them achieve the gender characteristics they identify with.
Clinical Guidelines: The World Professional Association for Transgender Health (WPATH) and the Endocrine Society have established guidelines to support healthcare providers in treating gender minority patients. These guidelines ensure that hormone therapy is prescribed and monitored safely, with an emphasis on improving the well-being of transgender individuals . PRISMA – reporting guidelines were used in the development of this protocol – driven report .
Study Selection and Follow-Up: Research on transgender patients undergoing hormone therapy typically involves follow-ups ranging from 3 to 12 months after starting treatment. Studies included in the analysis focused on participants who self-identified as transgender or had gender dysphoria, with a minimum of 10 participants. Monitoring during the follow-up period is crucial to assess both the effectiveness and potential risks of hormone therapy.
.Monitoring and Risks: It's important to monitor hormone therapy closely to avoid complications, such as a prolonged hypogonadal state (where hormone levels are too low). This can lead to bone mineral density loss, and excessive hormone exposure may result in other metabolic or physiological risks. Therefore, careful management of hormone dosing is vital for minimizing risks and ensuring optimal health outcomes. Treatments ( transmen and transwomen ) : gender affirming hormone therapy is feminizing or masculinizing hormone therapy through administration of exogeneous hormones . there are many variations in doses and types of hormones that are used to treat trans people . mainly two hormones are used i.e are Testosterone (male sex hormone ) and Estrogen ( female sex hormone )
1) Testosterone : testosterone therapy is used to suppress female secondary sex characteristics and masculinize transgender men. The therapy used resembles hormone replacement regimens used to treat natal men with hypogonadism and most of the preparations are testosterone esters . Testosterone is a key hormone used in masculinizing hormone therapy (MHT) for transgender men and transmasculine individuals. It plays a crucial role in promoting physical changes associated with male puberty and masculinity. Here are the primary effects of testosterone .
Masculinizing hormone therapy:
Masculinizing hormone therapy is used for trans men (assigned female at birth, transitioning to male). The primary hormone used is testosterone.
1. Testosterone helps to develop male secondary sexual characteristics, such as facial and body hair, deepening of the voice, increased muscle mass, and a more male-pattern fat distribution.
2. In some cases, additional medications may be used to suppress menstruation or prevent ovulation, but testosterone alone is often sufficient for most masculinizing effects.
Testosterone can be administered through injections (intramuscular or subcutaneous), gels, or patches.
|
Route |
Formulation |
Dosing |
|
Oral (not available in united states) |
Testosterone undecanoate |
160-240mg/day |
|
Parental (subcutaneous , intramuscular) |
Testosterone enanthate , cypionate |
50-200mg/week 100-200mg/10-14days |
|
Implant (subcutaneous ) |
testopel |
75mg/pellet |
|
Transdermal |
Testosterone gel(1%) testosterone patch |
2.5-10g/day 2.5-7.5mg/day |
testosterone undecanoate, an oral formulation of testosterone, is available in some European countries but is not commonly available in the United States. This is largely due to concerns regarding its first-pass metabolism when taken orally. Testosterone undecanoate is more lipophilic (fat-soluble) compared to other forms of testosterone, which allows it to be absorbed via the lymphatic system, bypassing the liver and reducing the impact of first-pass metabolism. In contrast, testosterone enanthate and testosterone cypionate are typically administered via intramuscular or subcutaneous injection in the U.S. to ensure adequate absorption and avoid the first-pass effect in the liver. Regarding progestogens, these are a class of hormones that include both natural progesterone (produced by the ovary) and synthetic compounds known as progestins. Progestins are often used in hormone replacement therapy (HRT) and contraception because they mimic the effects of natural progesterone in the body, although their properties can vary depending on their chemical structure.
Estrogen : hormone therapy for transgender women is intended to feminize patients by changing fat distribution , hair growth ,and reducing male pattern hair growth . estrogen is used in feminizing hormone therapy in transwomen .
Feminizing Hormones Therapy :
Feminizing hormone therapy (FHT) is typically used in the context of gender-affirming care for trans women (assigned male at birth, transitioning to female). The key hormones used in feminizing therapy are estrogen and anti-androgens (which lower testosterone levels).
1. Estrogen is the primary hormone used, which helps to promote the development of female secondary sexual characteristics such as breast development, redistribution of body fat, and skin softening.
2.Anti-androgens, like spironolactone or finasteride, block the effects of testosterone, helping to reduce male characteristics such as body hair and muscle mass.
Other forms of estrogen include estradiol, administered orally, transdermall (patches, gels), or via injection.
|
Route |
Formulation |
Dosing |
|
Oral |
Estradiol |
2-4 mg daily |
|
Parental ( subcutaneous , intramuscular ) |
Estradiol valerate |
5-30 mg every 2 weeks |
|
Transdermal |
Estradiol |
0.1-0.4 mg twice weekly |
|
Anti-androgens |
Progesterone medroxyprogesterone GnRH agonist (leuprolide) spironolactone |
20-60 mg po daily , 150mg IM every 3 months , 3.75-7.5 mg IM monthly , 100-200mg po daily |
progestogen and estrogen formulations used in hormone replacement therapy (HRT), particularly in the context of feminizing hormone therapy (HRT) for trans women. Here's a summary and clarification of the key points you mentioned:
1. Progestogen (Progesterone) Formulations:
- Progestogens, including synthetic progestins, are commonly administered via the oral route for hormone therapy.
- Oral progesterone can also be used vaginally, though this is often for non-FDA approved purposes.
- Progestogens are generally used in combination with estrogen for HRT, especially in individuals with an intact uterus to prevent endometrial hyperplasia and malignancy.
2. Estrogen in Feminizing Hormone Therapy: - Estrogen is central to feminizing hormone therapy, helping to induce physical changes like breast development, redistribution of body fat, and the reduction of male-pattern hair growth.
- Ethinyl estradiol and estradiol valerate are commonly used forms of estrogen. Estradiol (often in parenteral form like estradiol valerate) is a preferred formulation in some clinical settings due to its efficacy and side-effect profile.
- Estrogen alone is usually not sufficient to suppress androgens (male hormones) adequately in most trans women, so adjunctive anti-androgens (like spironolactone or GnRH agonists) are often prescribed.
- For individuals with an intact uterus, progestogens (progesterone or progestin) are typically added to estrogen therapy to protect the uterus from the risk of endometrial hyperplasia or cancer. This is because, without progestogen, unopposed estrogen could stimulate abnormal growth of the endometrium.
Administration : numerous estrogen and progestogen formulations are available for treating menopausal vasomotor symptoms . the various formulations of hormone replacement therapy have efficacy for treating vasomotor symptoms . they may be administered orally or transdermal through creams , sprays , patches , vaginal rings , or subdermal pellets .
Effects of estrogen and testosterone :
1.Testosterone:
Effects of Testosterone in Masculinizing Hormone Therapy:
1. Voice Deepening: Testosterone causes the vocal cords to thicken, leading to a deeper, more masculine voice.
2. Facial and Body Hair Growth: Increased testosterone leads to the growth of facial hair (such as a mustache or beard) and body hair (on the chest, arms, legs, etc.).
3. Muscle Mass and Strength: Testosterone helps increase muscle mass, resulting in more muscular physique and increased physical strength.
4. Fat Redistribution: Fat tends to redistribute away from the hips and thighs, moving more toward the abdomen, which creates a more traditionally masculine body shape.
5.Clitoral Enlargement: Testosterone can cause the clitoris to enlarge, a process known as clitoromegaly.
6. Increased Libido: Many individuals report an increase in sexual desire (libido) due to elevated testosterone levels.
7. Cessation of Menstruation: Testosterone typically leads to the cessation of menstruation (periods) within a few months of starting therapy.
8. Skin Changes : The skin often becomes thicker and oilier, which can lead to an increase in acne, particularly during the initial stages of therapy.
9. Mood and Emotional Changes: Testosterone can have mood-altering effects, often leading to increased feelings of assertiveness, confidence, and energy. However, some individuals may also experience mood swings or irritability.
Long-term Effects of Testosterone:
- Bone Density: Over time, testosterone therapy helps maintain or increase bone density, which can reduce the risk of osteoporosis.
- Fertility Changes: Testosterone can lead to reduced fertility, as it suppresses the production of sperm, though some individuals may retain fertility or may choose to preserve sperm before starting therapy.
-Cardiovascular Health: There may be an increased risk of certain cardiovascular conditions with long-term testosterone use, although more research is needed in this area.
Monitoring and Medical Considerations:
Transgender men on testosterone therapy require regular monitoring to ensure hormone levels remain within desired ranges and to track potential side effects, such as changes in liver function, red blood cell count, and cholesterol levels. Regular check-ups with a healthcare provider are important for managing therapy safely. Testosterone is typically administered through injections, gels, patches, or pellets, and the effects can vary depending on the method of delivery, dosage, and individual factors.
2 estrogen :
estrogen hormone therapy for transgender women plays a crucial role in feminizing the body. It helps achieve several key changes, including:
1. Fat distribution: Estrogen helps redistribute body fat in a more typically feminine pattern, such as increased fat in the hips, thighs, and breasts, while reducing abdominal fat.
2. Hair growth: Estrogen can slow or stop the growth of facial and body hair, which is often more prominent in individuals assigned male at birth. However, it is generally less effective in fully regrowing scalp hair or reversing male pattern baldness, though it can stabilize hair loss in some cases.
3. Breast development: Estrogen promotes the development of breast tissue, though the extent of growth varies from person to person, often depending on factors like age and genetics.
4. Skin changes: Estrogen can lead to softer, more supple skin by increasing collagen production.
Estrogen is typically combined with an anti-androgen, such as spironolactone, to reduce testosterone levels, further helping to achieve desired feminizing effects. It's important that hormone therapy is tailored to each individual and carefully monitored by a healthcare professional to manage side effects and ensure safety.
Risk factors :
1)Mental health problems
2)Experience with physical and verbal abuse
3)Social isolation
4)Low self-esteem
5)Poor relations
6)Discrimination
7)Acute myocardial infraction
8)Physical and sexual violence
9)Depression and anxiety
10)Harassment
CONCLUSIONS: The conclusions you've provided highlight several important points about hormone therapy (HRT) for both transgender individuals with gender dysphoria and for menopause management. Here’s a breakdown:
1. Hormone Therapy in Transgender People with Gender Dysphoria: Although hormone therapy for gender-affirming hormone therapy (GAHT) in transgender individuals shows promising short- to mid-term results in terms of effectiveness and safety, controlled trials specifically evaluating its impact on mental health and quality of life are lacking. However, the growing body of data supports the benefits of GAHT in improving the well-being of transgender individuals.
2. Hormone Replacement Therapy (HRT) in Menopause: In contrast, HRT for menopause is not recommended for routine use, particularly because of known long-term risks. The Women’s Health Initiative (WHI) study has reaffirmed these risks, which include an increased chance of cardiovascular disease, breast cancer, and stroke. Therefore, when prescribed for menopause symptoms, HRT should be used at the lowest effective dose for the shortest time possible. In summary, while GAHT in transgender individuals appears beneficial for mental health and quality of life, HRT in menopause must be carefully managed due to known long-term risks, and controlled trials are still needed for more comprehensive conclusions on GAHT.
REFERENCES
Akanksha Gade*, Akshada Suryawanshi, A Systematic Review on Hormone Replacement Therapy: Transgender, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 1086-1093. https://doi.org/10.5281/zenodo.14643771
10.5281/zenodo.14643771
