Transgender Hormone Treatment in Male-to-Female Transsexuals Annihilation of Male Characteristics
In male-to-female
transgender suppression of the original sex characteristics can be obtained by
compounds that exert directly or indirectly an antiandrogenic effect. Androgens
are for their production dependent on stimulation by the pituitary hormone
luteinizing hormone (LH) which, in turn, is stimulated by the hypothalamic
hormone luteinizing hormone-releasing hormone (LHRH). The biological action of
androgens is contingent on their interaction with hormone receptors in the
body's tissue cells. Interference with any of these mechanisms will lead to a
decline of the biological action of androgenic hormone. Some of the drugs that
will be listed have a dual action in this respect (Table 1).1. Suppression of gonadotropins (the pituitary hormones) that stimulate testicular and ovarian hormone production can be achieved by LHRH analogues: triptorelin and leuprorelin 3.75 mg/4 weeks are available as injectables. Their cost is prohibitive; a major side effect is hot flashes of the type that postmenopausal women experience. There is no reported experience with these drugs in transsexuals. Also cyproterone acetate, progestogens and high dose estrogens suppress gonadotropins by their negative feedback action. Progestogens are available in the form of medroxyprogesterone acetate (ProveraR) as a parenteral drug (150 mg/6 weeks) and Hydroxyprogesterone (Proluton) (250 mg/2 weeks) or oral drug (5-10 mg/day). They probably also interfere with the androgen receptor.TABLE 1. Hormones Used in Cross-Gender Hormone Treatment of Transsexualism
Antiandrogens LHRH analogues leuprorelin Lucrin depotR 3.75 mg/months s.c. triptorelin Decapepty1-CRR 3.75 mg/months i.m Interference with testosterone or DHT production Spironolactone Aldactone 100-200 mg/day p.o. finasteride not registered flutamide EulexinR 250 mg t.i.d., p.o. Antigonadotropic Cyproterone acetate Androcur 100-150 mg/day p.o. Hydroxyprogesterone Proluton depot 250 mg/2 weeks to 1000 mg/month i.m. medroxyprogesterone proveraR 5-10 mg/day p.o. Depo-ProveraR 150 mg/month i.m. FarlutaiR 5-10 mg/day p.o. Farlutal depotR 100 mg/month i.m. Androgen receptor blockers Cyproterone acetate Androcur 100-150 mg/day p.o. nilutamide AnandronR 300 mg/day p.o. Spironolactone Aldactone 100-200 mg/day p.o. Estrogens ethinyl estradiol Diane 35 100 µg/day p.o. Sucee 100 µg/day p.o. Yasmin 100 µg/day p.o. conjugated estrogens premarin 5-10 mg/day p.o. 17ß estradlol progynova 2-4 mg/day p.o. Progynon depot 10 mg/2 weeks to 100 mg/month i.m. Estraderm TTSR 50-100 µg/day trans dermally Oestrogel 75-150 µg/day trans dermally estriol SynapauseR 4-6 mg/day p.o. Androgens testosterone esters TestoylronR 250 mg/2 weeks 1.m. sustanonR 250 mg/2 weeks i.m. testosterone undecanoate AndrinlR 160-240 mg/day p.o.
2. interference with the production of testosterone or its conversion to the potent metabolite 5alpha-dihydrotestosterone (DHT) can be exercised by drugs like spironolactone (Aldactone) 100-200 mg/day. Finasteride is a potent 5 alpha-reductase inhibitor preventing the conversion of testosterone to DHT and therewith reducing its biological effect.
3. Drugs that interfere with receptor binding of androgens (or in the future with postreceptor mechanisms) have been used success-fully. Cyproterone acetate (Androcur) 100 mg/day orally or 300 mg/month intramuscularly and less effectively medroxyprogesterone acetate have also antigonadotropic action. The "pure" antiandrogens nilutamide (AnandronR) 300 mg/day and flutamide (Eulexin 250 mg, three times a day) are potent drugs. They are less suited as monotherapy since by their interference with the negative feed-back action of androgens, they stimulate gonadotropin production and subsequently androgen production. Spironolactone has also receptor-blocking properties.
Of all the above drugs side-effects have been reported. Some are inherent in the interference with the biological action of androgens like a reduction of muscle mass and power and of the hemoglobin content. Some patients will complain of loss of energy and vitality to straightforward depression. The antiandrogen we have extensively used is cyproterone acetate (100mg/day). Side effects encountered are those mentioned above. Our alternative drug is spironolactone. Several studies have demonstrated its efficacy in transsexuals and in hirsute women alike. It has also an antihypertensive effect, since the drug was designed as a diuretic.
We have limited experience with nilutamide and LHRH antagonists. Medroxy-progesterone acetate has been widely used in the USA also in sex offenders. It is a satisfactory drug also in the view of the mild side effects and the costs. A randomized double-blind clinical trial to establish the best suited antiandrogen compound in transsexuals has not been performed so far.
Following orchiectomy we try to reduce or terminate antiandrogen therapy. Sexual hair growth is clearly dependent on androgens for its initiation and it would be logical to believe that antiandrogens are redundant following orchiectomy. Though not verified by research data, patients claim that also after orchiectomy their sexual hair growth is still reduced by antiandrogens. Due to the much shorter life cycle of sexual hair on the trunk, arms and legs as compared to the face and the greater density of hair follicles in the beard area, beard growth is not reduced to a cosmetically acceptable degree by antiandrogens. Other measures like depilation by electrolysis are needed. Those subjects who are young enough to have no significant beard development or whose racial background provides them with little or no beard development, are not in need of antiandrogens for this purpose.
