General Health

Understanding Hormone Replacement Therapy in Transgenders

MedPiper Technologies and JournoMed had conducted a Webinar Series to “Improve Healthcare Access for Transgender and Sexual Minorities For The Doctors and By The Doctors” with IRIA Kerala- RakshaShakthi, Social Wings, IMA Kerala and CARBOn Day-2, 19th July, 2022, of the series, the speaker, Dr. Nisha Bhavani spoke about the topic of Endocrinology of Transgender Medicine. Dr Nisha Bhavani is a Clinical Professor and Endocrinologist from Amrita Hospitals.

To understand the endocrinology of Transgender Medicine, a basic understanding of sex and gender differentiation is needed. A phenotypical male has 46 XY chromosomes. Their gonads are testis and the internal genitalia are vas epididymis, prostate and seminal vesicles. The phenotypical female has 46 XX chromosomes, ovaries and uterus. The ovaries in the female produce estrogen and progesterone. From an embryological perspective, chromosomal sex determines the gonadal sex which determines the phenotypic sex.

An embryo develops from a single cell occurs after fertilization. The embryo up to 6 weeks has undifferentiated gonads. There is a SRY gene present in the XY chromosomes that dictates the gender of any individual. The SRY gene is found on the Y chromosome. The sex-determining Y protein produced from this gene acts as a transcription factor, which binds to specific regions of DNA and helps control the activity of particular genes. This protein starts processes that cause a fetus to develop male gonads (testes) and prevent developing female reproductive structures (uterus and fallopian tubes).

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Testis formation 

In the Y chromosome, the SRY gene dictates the gonads to become testis. The testis has Sertoli cells and Leydig cells. The Sertoli cells produce the anti-mullerian hormone (AMH) which causes Mullerian regression. (The Mullerian structures are the uterus and the vagina). When the testis produces AMH, the uterus and the vagina are regressed. Then, the Leydig cells of the testis produce testosterone which makes the internal genitalia male. This testosterone gets converted to dihydrotestosterone which makes the external genitalia looks like a phenotypical male.

Ovary formation

Ovary formation normally occurs in the absence of the SRY gene i.e. in XX or XO chromosomes. There are few genes which influence ovary development but the absence of the SRY gene mostly develops an ovary as it does not secrete AMH. Hence, the presence of Mullerian structures and no testosterone production in huge amounts makes the the external genitalia appear as a female.

The phenotypical sexual characteristics are assigned at birth. A misalignment of a gender different from that assigned at birth based on phenotypic sex is termed Gender dysphoria. Gender-determining genes are expressed much prior in the brain before the SRY gene enacts. Gender has a different origin in the brain when compared to sex determination. That is why gender dysphoria is termed a biological disease. Which is also why gender incongruent people vehemently oppose the inclusion of gender incongruency in sexual minorities and these are termed disorders of sexual minorities.

Gender Incongruence 

Gender incongruence (GI) is defined as a condition in which a person’s gender identity does not align with the gender assigned at birth. Persons with GI experience significant burdens in the DSM (Diagnostic and Statistical Manual of Mental Disorders) classification described as gender dysphoria (GD).

  • Gender incongruence is observed more in individuals with disorders of sexual development (DSD)
  • Greater transgender concordance is more among identical twins
  • Neuroanatomical differences are more associated with people of gender identity

Hormone Replacement Therapy in Transgenders

Hormone replacement therapy/transgender hormone therapy replaces natural hormones present in their bodies with the opposite sex hormones. It is prominently observed among transgender and transsexual people. It needs to be performed as per Endocrine Society and W Path guidelines. 

What to keep in mind regarding hormone replacement therapy?

  • Hormone replacement therapy improves long-term diseases and promotes a better quality of life. Efficient counselling from a multi-disciplinary team of doctors, mental health specialists, surgeons and social workers must be given before the treatment.
  • A mental health professional needs to establish the diagnosis for the concerned mental health disorder. Even patient expectations need to be met and clarified. The pros and cons of hormonal therapy need to be discussed.
  • Unmonitored treatment may involve huge risk and a strict follow-up is required. Future fertility options need to be discussed among people. 

Gender-affirming Hormone Therapy 

Gender-affirming hormone therapy for transgender patients includes administering estrogen, progesterone or testosterone hormones which helps the patients in affirming their gender, decreasing the symptoms of gender dysphoria and enhancing the patient’s life quality. The main aim is to induce physical changes that match gender identity.

Criteria for starting treatment 

The treatment must be planned and prioritized 6 months in advance. A proper informed consent needs to be duly signed and submitted. The minimum age limit for hormone replacement therapy is 14-18 yrs of age. It varies accordingly in different countries.

Male to female (MTF) Transition

Transwomen are injected with anti-androgens and estrogens. The most common anti-androgen is spironolactone needs to be administered orally. Oral estradiol is given as a supplement. Testosterone levels are maintained below the normal range even after gonadectomy. The estrogen doses need to be maintained. If the patient is on gonadotrophin-releasing hormone (GnRH) analogues, suppressing the leutinizing hormone (LH) and follicle-stimulating hormone (FSH) using Gram -ve Rod Adrenaline suppress the hormonal production from the testis. Anti-androgen therapy can be discontinued after gonadectomy.

Goals: The goal is to maintain feminization and reduce the hormonally induced male secondary sexual characters. Some factors are irreversible like the greater height, size and shape of hands, feet, jaws and pelvis can’t be reversed. Voice modulations can be done using speech therapy. 

Feminizing effects on Transgender females: Few feminizing effects in Transgender females include redistribution of body fat, decrease in muscle mass and strength, softening of skin/ decreased oiliness, decreased sexual desire, decreased spontaneous erections, male sexual dysfunction, breast growth, decreased testicular volume, decreased sperm production, decreased terminal hair growth, scalp hair and voice modulation

Monitoring the Male to Female therapy: A patient needs to be monitored every 3 months the first year and every 6 months thereafter. Testosterone should be below 50 mg/dl. Estradiol should not exceed the maximum (200 pg/ml). Spironolactone consumption develops hyperkalemia. Liver function tests, blood glucose and sugar tests need to be done. Even routine cancer screening needs to be performed. 

Female to male (FTM) Transition

Transmen are treated with testosterone. They don’t need anti-estrogens as they do very well with testosterone alone. Once they are on a full dose of testosterone every 2 weeks or once a week, patients are transferred to long-active testosterone undecanoate. A 1000 mg is given every 10-12 weeks. 

Goals: The goal is to stop menstruation, induce virilization, induce a male pattern of sexual and facial hair and change in voice and male physical contour parts. 

Masculinizing effects in Transgender males: Few masculinizing effects observed among transgender males are skin oiliness/acne, facial or body hair growth, scalp hair loss, increased muscle mass/ strength, fat redistribution, cessation of menses, vaginal atrophy, deepening of the voice, increased sexual desire, increase in growth of larnyx and clitoris etc. 

Persistent Mensus on Testosterone 

Though testosterone is commonly associated with men, it plays an instrumental role in women’s bodies throughout their menstruation. Testosterone is produced in lesser amounts in women and is largely produced in ovaries and adrenal glands. Methoxy progesterone ajesterate and oral progestin must be administered continuously. Treatment with a gonadotrophin-releasing hormone (GnRH) agonist must be administered 

Monitoring Female to Male therapy: Transmen must be monitored every 3 months the first year and every 6 months later. Transmen need to be monitored for testosterone, hematocrit, metabolic parameters, cancer screening (cervix/ breast/ ovary) and osteoporosis 

Conclusion

Understanding the endocrinology perspective in transgender medicine clarifies several dilemmas and doubts regarding the healthcare of Transgender Medicine. Cross-sex hormone therapy/transgender hormone therapy is one of the most implemented techniques by transexual and transgender people. Any sexual or hormonal replacement must be performed under medical supervision and the final goal is to satisfy the individual who underwent the surgery and thus it works for the better progress of the Transgender community. This also leads to a significant improvement in the psychological and psychosocial aspects of lives of Transgender individuals.  

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