The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy Estrogen mtf transsexuals or without cyproterone acetate in transgender women.
The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate.
The daily dose of conjugated equine estrogen was 0. Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different.
The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen and estrogen plus cyproterone acetate. In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.
Transgender women TW have a female gender identity and desire to live as a member of the female community 1. Cross-sex identification typically has an early
Estrogen mtf transsexuals and causes chronic suffering. To alleviate the distress associated with belonging to an undesired gender group, sex reassignment hormone therapy is indicated and must be preceded by a thorough psychological evaluation to establish the diagnosis of gender dysphoria 2.
The therapeutic process for TW includes three mainstays: During the process of changing from the male to the female phenotype, TW require the administration of cross-sex hormones to mitigate the phenotypic signs of the male biological sex and to develop female characteristics.
After hormone therapy, expected physical changes include breast development and the redistribution of body fat to a female pattern, as well as a decrease in facial hair growth, body hair growth, muscle mass, testicular volume and spontaneous erections 4.
The aim of hormone therapy in TW is to promote the development of female phenotypic characteristics using the lowest effective estrogen doses to maintain serum estradiol E2 and testosterone T levels "Estrogen mtf transsexuals" the normal range for women in the follicular phase of the menstrual cycle 35. The treatment regimen of TW usually consists of estrogen combined with a compound that suppresses androgen actions, such as spironolactone, finasteride, flutamide or cyproterone acetate CA 3.
Spironolactone has a synergistic effect with estrogen on physical changes 6. Finasteride and flutamide are rarely Estrogen mtf transsexuals the efficacy of finasteride is limited, and flutamide is associated with liver toxicity 7. CA is the most commonly used antiandrogen drug in Europe and South America. CA acts as a potent competitive antagonist of the androgen receptor and has additional progestational activity, inhibiting luteinizing hormone LH release 8.
Different estrogen compounds and routes of administration exist for cross-sex hormone treatment. The use of oral ethinyl E2 in transsexuals is associated with Estrogen mtf transsexuals increased risk of venous thromboembolism and death from cardiovascular events 9 The recommended estrogenic doses for feminization of TW, according to the Endocrine Estrogen mtf transsexuals guidelines, are usually three times higher than those used for hormone replacement therapy in postmenopausal women and are similar to those "Estrogen mtf transsexuals" in hypogonadal patients 3 We retrospectively analyzed the effects of lower doses of estrogen in TW on suppressing endogenous T and maintaining the physiological levels of E2 within the normal range for premenopausal women in the follicular phase.
All patients consulting in our Transsexual Unit with biochemical and hormonal data before and 6 months after therapy were invited to participate in this retrospective analysis, and of the 58 patients who were invited, 51 agreed to participate. The mean age at the first evaluation was All patients had a normal male phenotype 46, XY chromosome karyotypeand none of them had previously undergone an orchiectomy.
The daily doses of estrogen were 0. The fasting glucose levels were Estrogen mtf transsexuals with an automatic enzymatic colorimetric method using hexokinase Cobas Integra; Roche, Basel, Switzerland. Hoffmann-La Roche, Basel, Switzerland. The nonparametric Wilcoxon test was used to compare the hormone levels before and after treatment.
The nonparametric Mann-Whitney test was used to compare the different treatments. In this group of patients, four subjects received 0. Serum hormone levels of 51 transgender women before and after 6 months of low-dose estrogen therapy with or without cyproterone acetate.
Normal value for premenopausal women at the follicular phase of the menstrual cycle: Serum hormone levels after 6 months of treatment with different doses of conjugated equine estrogen alone or with cyproterone acetate in transgender women.
Thirty-seven subjects received 0. After comparing these two CEE subgroups, we observed that both treatments were able to suppress the T levels to within the normal female range 22 vs The values were Serum hormone levels in transgender women after 6 months of conjugated equine estrogen therapy with or without cyproterone acetate therapy.
TW generally have a psychological need to increase estrogen replacement doses to acquire a female phenotype as soon as possible. A higher estrogen dose is associated with an increased risk of venous thromboembolic disease, pulmonary embolism, myocardial infarction, stroke, hormone-related tumors and adverse liver effects In addition to these common side effects of high-dose estrogen therapy, increases in PRL levels and even prolactinoma development have been described in TW 18 - The ideal dosage of cross-sex hormones is still unknown because randomized controlled trials in this specific transgender population are not available.
Estrogen mtf transsexuals of estrogens, variability of their measurement and different routes of administration make the standardization of therapeutic regimens difficult. Long-term follow-up studies of hormone treatment in transsexuals and of hormone replacement therapy in biological females are used to guide cross-sex hormone therapy in TW 3.
The use of a synthetic estrogen, ethinyl E2, in a large cohort of transsexuals has been associated with an increased risk of cardiovascular and thromboembolic events. Interestingly, the vast majority of these "Estrogen mtf transsexuals" events occur during the first year of estrogen treatment, and the risk is higher in patients older than 40 years 9 Natural estrogens are safer options than synthetic estrogens for cross-sex hormone treatment 11 - Transdermal preparation is the safest form of estrogen administration, especially in transsexual patients who smoke or have diabetes because the transdermal preparation does not influence protein, lipoprotein or triglyceride synthesis, thereby reducing the thrombotic cardiovascular risks 3.
In our hospital, transsexual patients are treated by a multidisciplinary group and receive psychological support before and after surgery.
The psychological support controls the anxiety of the patients as they develop the female phenotype and allows us to treat our patients with the lowest Estrogen mtf transsexuals doses necessary to normalize androgen and estrogen levels. This study is the first to evaluate the use of low doses of estrogens in TW. We have demonstrated that low estrogen doses alone or with CA are effective toward maintaining androgen suppression and serum E2 within the normal follicular-phase range.
Evaluations of the effects of low-dose estrogen therapy Estrogen mtf transsexuals physical changes, namely, breast development, facial hair growth, body hair growth and body fat redistribution, were not possible in our patient population because all of the patients reported prior use of other estrogen formulations without medical supervision for a variable period of time.
However, the maintenance of estrogen levels in the normal female range suggests that low-dose "Estrogen mtf transsexuals" therapy may be able to promote the satisfactory feminization of these patients.
The facial hair response to hormonal treatment in transsexuals, even at high estrogen doses, is very poor and often requires complementary cosmetic treatments such as laser treatments and electrolysis.
The use of CA is especially important to alleviate androgenic signs and symptoms such as the male pattern of facial and body hair Estrogen mtf transsexuals the undesired spontaneous penile erections frequently reported by TW.
In our analysis, we noted that CA was not critical for achieving androgen suppression and that estrogen alone, even at low doses, was effective toward suppressing the hypothalamic-pituitary-testicular axis 8 Even so, we observed that the regimen comprising estrogen plus CA achieved a more potent suppression of LH levels than the regimen containing estrogen Estrogen mtf transsexuals from 6.
In our clinical practice, we avoid daily doses higher than 50 mg of CA because of its potential metabolic side effects, including weight gain and high blood pressure. We observed that the GGT levels were higher in the group receiving estrogen plus CA than in the group receiving estrogen alone, although the both groups presented with GGT levels in the normal range.
In our cohort, the estrogen levels before and after cross-sex hormone treatment were not significantly different. The conversion of male levels of T to estrogen before treatment was similar to that achieved by the low-dose estrogen treatment Estrogen-induced increases in PRL levels in many physiological conditions, such as pregnancy and puberty, are well known, and a mild increase in PRL levels in TW has been described after estrogen therapy Similarly, higher PRL levels were identified in our cohort after low doses of estrogen therapy.
Although these levels were not statistically significant in the group that received estrogen alone, a significant increase was observed in the group receiving estrogen plus CA. Our results demonstrated that the different doses of CEE 0.
Additionally, we observed that the two different doses of CEE had similar effects on hormone levels after 6 months of treatment.
However, these data should be regarded with caution because the number of individuals in each subgroup is very small, thus reducing the statistical power of the sample. In conclusion, in our sample of TW, lower estrogen doses than those usually prescribed for these subjects were able to adjust the T and E2 levels to the physiological female range, avoiding the risks of high estrogen doses. Cunha FS and Sircili MH were responsible for the acquisition and analysis of data, and manuscript drafting.
No potential conflict of interest was reported. National Center for Biotechnology InformationU. Journal List Clinics Sao Paulo v. Published online Apr Author information Article notes Copyright and License information Disclaimer. Received Jul 16; Accepted Nov 8. Biochemical analysis The fasting glucose levels were determined with an automatic enzymatic colorimetric method using hexokinase Cobas Integra; Roche, Basel,
Estrogen mtf transsexuals. Statistical analysis The nonparametric Wilcoxon test Estrogen mtf transsexuals used to compare the hormone levels before and after treatment.
Table 1 Serum hormone levels of 51 transgender women before and after 6 months of low-dose estrogen therapy with or without cyproterone acetate. Open in a separate window.
Table 2 Serum hormone levels after 6 months of treatment with doses of conjugated equine estrogen alone or with cyproterone acetate in transgender women.
Table 3 Serum hormone levels in transgender women after 6 months of conjugated equine estrogen therapy with or without cyproterone acetate therapy.
Footnotes No potential conflict of interest was reported. The DSM diagnostic criteria for gender identity disorder in adolescents and adults. Endocrine treatment of transsexual persons: "Estrogen mtf transsexuals" Clin Endocrinol Metab. Endocrine treatment of transsexual people: Care of transsexual persons. N Engl J Med. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism.
Medical management of adult transsexual persons. Long-term treatment of transsexuals with cross-sex hormones: Mortality and morbidity in transsexual patients with cross-gender hormone treatment.
Mortality and morbidity in transsexual subjects treated with cross-sex hormones. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones.