37.2: Feminizing Hormonal Therapy
By the end of this section, you should be able to:
- 37.2.1 Identify the characteristics of feminizing hormonal drugs used for transgender and nonbinary therapy.
- 37.2.2 Explain the indications, actions, adverse reactions, and interactions of feminizing hormonal drugs used for transgender and nonbinary therapy.
- 37.2.3 Describe nursing implications of feminizing hormonal drugs used for transgender and nonbinary therapy.
- 37.2.4 Explain the client education related to feminizing hormonal drugs used for transgender and nonbinary therapy.
The hormones used for female reproductive health, which are covered in Reproductive Health Drugs, are also discussed in this chapter; complete information for the drugs can be found there. Discussion in this chapter focuses on use of the medications for developing female secondary sex characteristics in individuals who were assigned male at birth and choose to undergo male-to-female (MTF) transition . These sex characteristics include fat redistribution around the hips, skin softening and decreased oiliness, growth of breast tissue, decreased muscle mass and strength, loss of facial hair, decreased libido and ejaculation volume, and decreased testicle size (Figure 37.2). The adverse effects of female hormone therapy are related to cardiovascular conditions such as myocardial infarction, stroke, and thromboembolic events. However, studies of transgender individuals are still limited in number, and more research is needed to explore the effects of female hormones on male clients (Deutsch, 2016; Hembree et al., 2017; Ramsay & Safer, 2023; Unger, 2016). Further transition would include surgery to remove the testes, as well as other feminizing surgical procedures (Mount Sinai, n.d.-b).
Safety Alert
Spironolactone
Spironolactone may cause hyperkalemia because it is a potassium-sparing medication. The nurse should monitor the client’s potassium levels and cardiac and renal function. Potassium may be found in intravenous fluids, salt substitutes, and some fruits and vegetables (including oranges, bananas, raisins and other dried fruits, and dark green and yellow vegetables).
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.
| Drug | Routes and Dosage Ranges |
|---|---|
| Conjugated estrogens | 2–6 mg/day orally. |
| 17-beta-estradiol | 2–4 mg /day orally. |
| Estradiol valerate | 5–30 mg every 2 weeks intramuscularly. |
| Estradiol cypionate | 2–5 mg/week intramuscularly. |
| Estradiol patch | 0.1–0.4 mg twice weekly transdermally. |
Adverse Effects and Contraindications
A major contraindication for estrogen is a personal or family history of blood clots in the leg (deep vein thromboses) or lungs (pulmonary emboli). Estrogen should be used cautiously in clients who smoke, have obesity, or have hypertension (Mayo Clinic, 2021a; T’Sjoen et al., 2019; Unger, 2016).
Adverse effects of estrogen can include major cardiovascular problems (cardiac disease, elevated cholesterol, stroke, and hypertension), elevated prolactin levels, nipple discharge, and infertility (Mayo Clinic, 2021a; Milionis et al., 2022; T’Sjoen et al., 2019; Unger, 2016).
Table 37.3 is a drug prototype table for estrogen-based feminizing hormones featuring 17-beta-estradiol in the context of MTF transgender treatment. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Estrogen (hormone) Mechanism of Action Decreases testosterone production |
Drug Dosage
2–4 mg/day orally (may vary depending on specific type of estrogen). |
|
Indications
Aids in MTF transition Therapeutic Effects Development of female sex characteristics: Increased breast size Weight gain and fat redistribution Softer, less oily skin Decreased facial hair Decreased muscle mass Decreased libido Decreased testicle size |
Drug Interactions
Ketoconazole Barbiturates Carbamazepine Phenytoin Penicillins Tetracyclines Rifampin St. John’s wort False unicorn root Red clover Wild yam Food Interactions Grapefruit and grapefruit juice |
|
Adverse Effects
Blood clots (deep vein thromboses, pulmonary emboli) Increased triglycerides Stroke Myocardial infarction Hypertension Increased serum potassium Increased serum prolactin Nipple discharge Weight gain Infertility Type 2 diabetes Increased risk of hormone receptor–positive breast cancer |
Contraindications
Estrogen-sensitive cancer (prostate) Active or history of thrombophlebitis or thromboembolic problems Cardiovascular disease Smoking Hypersensitivity |
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).
|
Drug Class
Progestin (female hormone) Mechanism of Action Antiandrogenic effect through central blockade of gonadotropins |
Drug Dosage
Dosages vary in the literature. |
|
Indications
Aids in MTF transition Therapeutic Effects (Based on anecdotal information from clients and providers) Improved breast and/or areolar development Improved mood Increased libido |
Drug Interactions
No significant interactions Food Interactions Grapefruit and grapefruit juice (inconclusive) |
|
Adverse Effects
Information is inconclusive. |
Contraindications
History of thrombotic events Cardiac, renal, or liver disease |
FDA Black Box Warning
Estrogen Plus Progestin Therapy
The Women’s Health Initiative studies demonstrated an increased risk of invasive breast cancer in clients treated with estrogen plus progestin therapy.
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.
|
Drug Class
GnRH agonist Mechanism of Action Decreases testosterone production and lessens the development of male secondary sex characteristics |
Drug Dosage
3.75–7.5 mg intramuscularly monthly. |
|
Indications
Aids in MTF transition Therapeutic Effects Suppresses puberty and development of secondary sex characteristics |
Drug Interactions
No significant interactions Food Interactions No significant interactions |
|
Adverse Effects
Information is inconclusive; may cause the following: Decreased bone density Impaired fertility Hot flashes Acne Emotional lability Cognitive issues Prolonged QT/QTc interval or other cardiac issues (irregular rhythms, heart failure) |
Contraindications
Hypersensitivity History of thrombotic events Hormone-sensitive cancers Hyperglycemia and increased risk for diabetes Prepuberty (client should reach Tanner stage 2 before using the drug) |
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).
Safety Alert
Finasteride
Females of childbearing age, particularly those who are pregnant, should not handle finasteride, especially if the tablets are broken. The medication can be absorbed and negatively affect genital development in a male fetus.
Adverse Effects and Contraindications
Finasteride is contraindicated for use in female clients and during pregnancy. Additionally, those who are pregnant should not handle crushed or broken pills because finasteride can cause abnormalities of the external genitalia in a male fetus. Adverse effects may include breast tenderness, testicular pain, depression, breast cancer, and liver toxicity (DailyMed, Finasteride , 2018; Unger, 2016).
Table 37.6 is a drug prototype table featuring finasteride. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
5-alpha-reductase inhibitor Mechanism of Action Inhibits the conversion of testosterone to 5-alpha-dihydrotestosterone |
Drug Dosage
1–5 mg orally daily. |
|
Indications
Aids in MTF transgender transition Therapeutic Effects Shrinking of prostate gland Decreased libido Erectile dysfunction Decreased volume of ejaculate Breast enlargement |
Drug Interactions
No significant interactions Food Interactions No significant interactions |
|
Adverse Effects
Breast tenderness Testicular pain Breast cancer Depression Liver toxicity |
Contraindications
Females Pregnancy Children Caution: Liver disease because the drug is metabolized in the liver |
Clinical Tip
Target for Hormone Therapy
A reasonable target for hormone therapy for transgender female clients is to reduce testosterone levels to the typical range of 30–100 ng/dL found in cisgender female individuals without producing an above-normal level of estradiol (less than 200 pg/mL). This is accomplished by administering an antiandrogen and estrogen.
(Source: Boston University, n.d.)
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.
Client Teaching Guidelines
The client taking a feminizing hormone should:
- Know the names, actions, effects, side effects, contraindications, precautions, and drug and food interactions related to their medications.
- Understand the schedule for medication administration: time, dosage, and route.
- Understand the importance of keeping all medications away from children.
- Be able to self-administer parenteral or transdermal medications.
- Notify the health care provider regarding any serious or particularly uncomfortable adverse effects, including hives, swelling of the lips or mouth, severe mood changes, irregular heart rhythm, muscle cramps, and seizures.
- Be aware of fertility considerations and the available options.
- Continue to attend wellness visits and schedule routine diagnostic procedures such as for prostate and breast cancer prevention.
- Be aware of community resources for transgender individuals such as health care and support groups.
Special Considerations
Resources
These resources may be helpful for transgender, nonbinary, and LGBTQ+ clients:
- American Bar Association Transgender Resources
- GLAAD
- Human Rights Campaign
- National Center for Transgender Equality
- Trans Lifeline
In addition to these online resources, most campuses have a diversity center open to all students. Larger teaching hospitals often have resources for clients who are experiencing gender issues. Public health entities, such as local health departments, also may have assistance available.
Link to Learning
The documentary Secret Intersex explores the lives of individuals who were born with ambiguous genitalia or other sexual characteristics. Parents must choose how to raise their children and decide whether and when to pursue medical treatment such as hormone therapy and surgery.