1. Persistent, well-documented gender dysphoria
2. Capacity to make a fully informed decision and to consent for treatment
3. Age of majority in a given country
4. If significant medical or mental health concerns are present, they must be reasonably well controlled
Moreover, before starting treatment, it is recommended to evaluate and address conditions that can be exacerbated by this treatment, as thromboembolic diseases (very high risk), macroprolactinoma, severe liver dysfunction, breast cancer, coronary artery disease, cerebrovascular disease, and severe migraine headaches (moderate to high risk) [6]. Pretreatment schedule is reported in Table 10.2.
Table 10.2
Monitoring schedule for MtF GD individuals
Pretreatment |
Physical examination: weight, blood pressure, waist, body mass index, hair distribution, balding pattern |
Fasting lipid, renal and liver function, glucose, glycosylated hemoglobin, complete blood count, serum estradiol, testosterone, prolactin |
For those taking spironolactone: electrolytes |
If osteoporosis risk exists (previous fracture, family history, glucocorticoid use, prolonged hypogonadism), in older than 60 years: bone mineral density according to natal sex |
During first year of treatment, every 3 months |
Physical examination: weight, blood pressure, waist, body mass index, hair distribution, balding pattern, breast development |
Fasting lipid and liver function, glucose, serum estradiol, testosterone, prolactina |
Electrolytes (for those taking spironolactone) |
During second year of treatment, every 6 months |
Physical examination: weight, blood pressure, waist, body mass index, hair distribution, balding pattern, breast development |
Fasting lipid and liver function, glucose, glycosylated hemoglobin, complete blood count, hemoglobin, serum estradiol (ideal <200 pg/ml) and testosterone (ideal <55 ng/dl), prolactina |
Electrolytes (for those taking spironolactone) |
PSA and digital rectal prostate exam (in older than 50 years) |
After genital reassignment surgery (when requested), every 12 months |
Physical examination: weight, blood pressure, waist, body mass index, hair distribution, balding pattern, breast development |
Fasting lipid and liver function, glucose, glycosylated hemoglobin, complete blood count, hemoglobin, serum estradiol (ideal <200 pg/ml) and testosterone (ideal <55 ng/dl), prolactinb |
Additional screening |
Bone mineral density according to natal sex (if osteoporosis risk exists) |
PSA, digital rectal prostate exam according to establish guidelines for biological sex |
Mammogram/breast ultrasound according to establish guidelines for assigned sex |
Cessation of tobacco use should be strongly recommended, in order to avoid an increased risk of cardiovascular complication and thromboembolism [6].
10.3 Cross-Sex Hormonal Regimens in MtF Individuals
10.3.1 Antiandrogens Treatment
Several agents are commercially available to inhibit androgen secretion or action. The most commonly used drug in Europe is cyproterone acetate (CPA, 50 mg once or twice daily, see also Table 10.3), a progestational agent with antiandrogenic properties [6, 12, 13]. Spironolactone (50–100 mg twice daily), a diuretic with antiandrogenic proprieties – mostly used in the United States (where CPA is not available) – has antiandrogenic effects by directly inhibiting testosterone secretion and androgen binding to the androgen receptor [14, 15].
Table 10.3
Cross-sex hormone treatment protocols in MtF GD individuals
Antiandrogens regimens | |
Cyproterone acetate | 50–100 mg/d |
Spironolactone | 100–200 mg/d |
GnRH analogs | 3.75 mg sc/monthly or 11.25 mg sc/3 months |
Estrogens regimens in MtF GD individuals | |
Oral estradiol | 2–6 mg/d |
17-β estradiol patch | 100–400 mcg/24 h (changing the patch as directed once or twice weekly) |
17-β estradiol hemihydrate gel | 2 mg twice daily |
17-β estradiol gel | 3–4.5 mg daily |
GnRH agonists, injected monthly (3.75 mg) or every 3 months (11.25 mg), could be also considered a good alternative for their efficacy in reducing testosterone levels and their low risk of adverse effects [16]. However, they are extremely costly, and therefore their use is limited.
Nonsteroidal antiandrogen, such as flutamide (50–75 mg/day), which blocks binding of androgens to the androgens receptor, can be theoretically used; it induces gonadotropin secretion and, consequently, increases testosterone and estradiol levels (which can be desirable in this circumstance). However, for its liver toxicity and undemonstrated efficacy in GD population, its use is not recommended [6].
Finally, finasteride (5 mg daily) – which inhibits the conversion of testosterone to 5α-dihydrotestosterone – can be used as additional antiandrogen, particularly to slow male pattern balding.
10.3.2 Estrogens Treatment
A wide range of estrogenic compounds can be used (see also Table 10.3). Typical GD estrogen dosage needs to be two to three times as high as the recommended doses for hormone replacement therapy in postmenopausal women [14].
Oral or transdermal 17-beta-estradiol is the treatment of choice. As transdermal estradiol seems to have a lower thromboembolic risk, it should be particularly considered for individuals which are at highest risk for thromboembolic events (i.e., those older than 40 years, smokers, and/or with diabetes or liver disease) [6, 17, 18].
As oral ethinyl estradiol has been reported associated with a 20-fold increased risk of venous thrombosis – particularly in subjects over 40 years [19] – and with a threefold increase in cardiovascular mortality [9], it should be avoided. Moreover, the impossibility to monitor its blood levels represents an additional important and practical limitation for its use.
Many patients ask for injectable estrogens, but avoidance of intramuscular dosing is rationalized by the prolonged time to reach steady state and the potential for abuse of this formulation [14].
Moreover, often clients believe that progestins have a fundamental role for their feminization, particularly for breast development. However, they should have informed that progestagens’ role is – in natal female – to prepare uterus for conception and breast for lactations. No evidences of additional feminization effects are available in transsexual populations [4, 7]. In addition, they have many side effects of which patients should be aware of, e.g., water retention and consequent elevation of blood pressure and weight gain, detrimental lipid changes, and depression [8]. Last but not least, breast cancer and cardiovascular diseases have been reported when used in postmenopausal women together with estrogens [20].
10.3.3 Approach in Specific Conditions
10.3.3.1 Partial Sex Reassignment
In clients wishing only partial sex reassignment, with only antiandrogens, it is fundamental to perform a careful medical supervision in order to mitigate the consequence of the induced hypogonadism, e.g., osteoporosis, obesity, loss of muscle mass and strength, cardiovascular risk, and depression.
10.3.3.2 After Genital Reassignment Surgery
On the other hand, if the patients choose to undergo genital reassignment surgery, estrogen treatment should be carried on, in order to avoid signs and symptoms correlated to hypogonadism and to avoid osteoporosis. Some subjects still complain for male typical sexual hair growth, and antiandrogens may remain effective, although their dose may be reduced compared to presurgery.
10.3.3.3 Prior and After an Elective Surgical Intervention
It is advisable to stop CHT 3–4 weeks prior to any elective surgical intervention, e.g., genital reassignment surgery. In fact, immobilization is a thrombogenic risk factor, and sex steroids may aggravate this risk. Once fully mobilized following the surgical procedure, the client may resume hormonal therapy [21].
10.3.3.4 Postmenopausal Age
Up to now, there is no consensus if CHT has to be stopped when client gets older, mirroring the postmenopausal milieu, and no data are available on this regard [7].
10.4 Adequacy Treatment Monitoring
According to the Endocrine Society guidelines [6], clinical and laboratory monitoring have to be performed every 3 months during the first year of CHT and then every 6–12 months, as reported in Table 10.2.
Routine cancer screening is recommended as in non-transsexuals individuals (breast, colon, prostate [6]).
Both estradiol and testosterone levels have to be monitored regularly in order to avoid supraphysiological levels and to minimize the risk of adverse effects [4].
Adequacy of estrogens levels could be monitored by measurement of serum estradiol levels when oral, transdermal, and intramuscular estradiol or its esters are used, but not with conjugated or synthetic estrogens. As daily stable levels are achieved after 1 week of therapy with transdermal or oral formulation, serum levels may be checked at any time during the treatment. When injectable formulations are used, serum levels have to be sampled in the middle between two injections [4]. Theoretically, serum estradiol should be maintained at the mean daily for premenopausal women (<200 pg/ml), and testosterone levels should be in the female range (<55 ng/dl) [6]. Treatment doses should be adjusted accordingly. Moreover, body feminization changes should be monitored in order to guide treatment [4].
10.5 Efficacy of CHT in MtF Individuals
10.5.1 Breast Formation
Increase in breast size usually begins within the first 3–6 months after initiation of CHT and achieves the maximum by 2 years of therapy [22]. It has been reported, from clinical experience, that only in one-third of patients it reaches cup B and that this is quantitatively satisfactory in 40–50 % of the subjects [23]. The remaining 50–60 % judge their breast formation as insufficient [23]. This may be also the consequence of the fact that the attained size could be disproportional to the male-typical chest and height of the subjects. Therefore, many clients ask for augmentation mammoplasty.
10.5.2 Skin
Often clients complain of dry skin and brittle nails, as a result of decreased sebaceous glands activity due to androgen deprivation [24].
10.5.3 Body Hair
CHT induces a reduction of sexual hair growth and hair shaft diameter. This decrease reaches a maximum after 4 months treatment with CHT, but then does not progress further [13]. Usually hair become thinner and less pigmented [24]. However, facial hairs are resilient to CHT particularly in Caucasian clients, and usually additional measures – electrolysis or laser treatment – to eliminate beard are almost always necessary. Electrolysis is effective but painful and potentially scarring. Laser is less uncomfortable but is most effective for people with dark hair.
Sexual hair on others parts of the body responds more satisfactorily, usually within 1–2 years of CHT, and, then, only waxing is required [24].
10.5.4 Body Composition
A decrease of lean body mass and an increase of subcutaneous fat deposits are observed [25]. It is therefore fundamental to encourage a healthy lifestyle.
10.5.5 Voice
CHT has no effects on voice on MtF individuals. Speech therapy can be considered an option to develop a voice within the frequency ranges for a biologic female [26]. Alternatively, laryngeal surgery may be considered in order to change the pitch of the voice, even it reduces its range.
10.5.6 Testes and Prostate
Testes and prostates become atrophy. Sometimes testis may cause discomfort as they enter in the inguinal canal.
10.5.7 Sexual Effects
Decrease of libido and spontaneous erections and male sexual dysfunction, often desired by patients, are usually observed within 1–3 months after starting CHT [6].
10.6 Adverse Effects of CHT
Serious adverse effects have been reported with long-term CHT.
10.6.1 Bone Health
Different studies have reported that estrogens are able to preserve adequately bone mineral density in MtF individuals [27, 28]. However, recently, some authors have observed a high prevalence of osteoporosis and osteopenia in their samples, which may be also related to an inadequate estrogenization of patients studied [9, 29].
10.6.2 Cardiovascular Health
In the general population, males have a higher cardiovascular risk when compared to females, and the risk in women increases only with cessation of estrogen production with menopause [23]. However, protective effects of exogenous estrogens have been refuted by the large randomized trials (Heart and Estrogen/Progestin Replacement Study (HERS) and the Women’s Health Initiative) [32].
Related posts:
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Follow-Up of Patients After Male-to-Female (Mtf) Sex Reassignment Surgery (SRS)
The Hot Questions of Prepubertal Gender Dysphoria in Girls
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Imaging
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