37.2 Feminizing Hormonal Therapy

Spironolactone

Spironolactone is a nonspecific aldosterone blocker. Its primary use is as a potassium-sparing diuretic to manage hypertension. However, its action of blocking male sex hormone receptors, the androgen receptors, decreases the production of testosterone, the male hormone responsible for secondary sex characteristics (DailyMed Spironolactone, 2023; Deutsch, 2016; Hembree et al., 2017; Mayo Clinic, 2021a; Ramsay & Safer, 2023; Unger, 2016). Spironolactone is used for 4–8 weeks alone, and then estrogen is usually added. Spironolactone can cause impotence and gynecomastia (breast tissue enlargement) in males, a desired effect for males transitioning to females.

Estrogen

The purpose of estrogen is to continue the development of secondary female sex characteristics. Estrogen works through a negative feedback loop to suppress gonadotropin secretion from the pituitary gland and results in reduced androgen production. Usually, estrogen alone will not achieve sufficient androgen control. Thus, antiandrogenic therapy, in the form of spironolactone, may need to be added to the client’s medication regimen. Although this may seem contrary to the information regarding spironolactone—that is, starting spironolactone first and then adding estrogen—both regimens are acceptable. The specific medication regimen depends on the individual’s needs (Deutsch, 2016; Hembree et al., 2017; Mayo Clinic, 2021a; Ramsay & Safer, 2023; Unger, 2016).

Clients will notice the onset of these characteristics: smaller testicles; fewer erections and a decrease in ejaculation; decreased libido; decreased male pattern baldness; breast development; softer, less oily skin; less muscle mass; and more body fat. These changes will usually begin 1–6 months after treatment starts. The full effect will take 2–3 years (Deutsch, 2016; Hembree et al., 2017; Mayo Clinic, 2021a; Ramsay & Safer, 2023; T’Sjoen et al., 2019; Unger, 2016).

Estradiol is the most potent form of estrogen and is naturally produced in the body. Estradiol is extremely beneficial prior to menopause and for use as postmenopausal hormone replacement therapy. It provides significant protection against cardiovascular disease and osteoporosis. It has been shown to work well in MTF transgender therapy also. Estradiol can be administered orally, parenterally, and transdermally.

Table 37.2 lists common estrogen-based feminizing hormones and typical routes and dosing for adult clients.

Progesterone

Progesterone is a hormone that is classified as a progestin and aids in the development of secondary female sexual characteristics. Progestins are metabolized by the liver and excreted in urine. Contraindications, precautions, and adverse events are similar to those for estrogen. (See Reproductive Health Drugs for more information about progesterone).

Progesterone can cause fluid retention and may adversely affect conditions that are worsened by fluid retention, including cardiovascular and renal diseases, asthma, and migraine headaches (DailyMed, Medroxyprogesterone, 2020). Clients undergoing MTF transition sometimes request progesterone to enhance breast enlargement. However, because there is no evidence that this is effective and because this treatment involves risks, progesterone therapy is not routinely used in transgender treatment (Hembree et al., 2017; T’Sjoen et al., 2019).

Table 37.4 is a drug prototype table for progesterone in the context of MTF transition treatment. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications. Most information regarding the use of progesterone in MTF transgender treatment is inconclusive because few studies have been conducted in this context (Deutsch, 2016; Hembree et al., 2017; Milionis et al., 2022; Ramsay & Safer, 2023; T’Sjoen et al., 2019).

Gonadotropin-Releasing Hormone Analogs

The action of gonadotropin-releasing hormone (GnRH) analogs decreases the amount of testosterone produced, which lessens the development of male secondary sex characteristics. GnRH analogs have been used for transitioning transgender adults. They may allow the client to reduce the dose of estrogen and eliminate spironolactone from the treatment regimen. However, GnRH analogs tend to be more expensive than spironolactone and may not be covered by medical insurance. Additionally, GnRH analogs require repeated injections or multiple daily nasal sprays. For these reasons, GnRH analogs may not be the best choice for some clients (Deutsch, 2016; Hembree et al., 2017; Hruz, 2020).

One of the primary benefits of GnRH analog therapy is that once therapy is discontinued, the sex characteristics of the sex assigned at birth return. Therefore, a client who decides not to pursue transgender treatment will not have permanent changes to their body (Hembree et al., 2017; Hruz, 2020).

On the other hand, few studies have been completed regarding the use of GnRH analogs. Thus, some of the long-term effects, adverse effects, exact dosing, and best administration method have not been determined. Adverse effects that appear to be related to GnRH analog therapy include decreased bone density, diminished adult height, and impaired spatial memory (Hembree et al., 2017; Hruz, 2020).

Table 37.5 is a drug prototype table for GnRH analogs featuring leuprolide. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Finasteride

Finasteride is a 5-alpha-reductase inhibitor essential for the development of male sex characteristics before birth, such as the formation of external genitalia. It acts to inhibit the conversion of testosterone to 5-alpha-dihydrotestosterone. Finasteride does not block the production or action of testosterone. Thus, it has less antiandrogenic effect than spironolactone does (DailyMed, Finasteride, 2018; T’Sjoen et al., 2019). However, it is a good choice for individuals who are unable to take spironolactone because of contraindications or other physiologic concerns or who lack the finances or insurance coverage to obtain spironolactone (Deutsch, 2016; Unger, 2016).

The therapeutic effects of finasteride in the context of MTF transition are the same as the adverse effects when it is used for male pattern hair loss. It results in decreased libido, decreased ejaculation, erectile dysfunction, and breast enlargement. The daily dose is 1–5 mg orally. Finasteride has no confirmed drug or food interactions (DailyMed, Finasteride, 2018); T’Sjoen et al., 2019; Unger, 2016).

Nursing Implications

The nurse should do the following for clients who are taking feminizing hormones:

• Assess baseline health, including underlying medical conditions, current medications, and pertinent laboratory and diagnostic results.
• Be cognizant of the client’s feelings, values, and culture in order to render sensitive care.
• Monitor for feminizing and adverse effects every 3 months for the first year and then every 6–12 months and as needed for problems.
• Monitor serum testosterone and estradiol levels at follow-up visits, with a practical target in the female range (testosterone, 30–100 ng/dL; estradiol, less than 200 pg/mL).
• Monitor prolactin and triglyceride levels before the client starts hormone therapy and at follow-up visits.
• Monitor potassium levels if the client is taking spironolactone.
• Perform bone mineral density screening before the client starts hormone therapy if they are at risk for osteoporosis. Otherwise, start screening at age 60 or, if sex hormone levels are consistently low, earlier.
• Screen MTF clients for breast and prostate cancer appropriately.
• Ensure that the client understands issues related to family planning and has had an opportunity to meet with a family planning specialist to discuss options because of the fertility-related effects of these drugs. Resources are available for various options, such as freezing sperm or donating sperm to a partner or another person who will carry a pregnancy.
• Ensure that the client is aware of and has access to resources such as community organizations, specialty clinics and hospitals, and support groups.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.