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Annoying Side Effect Of Testosterone Replacement Therapy
Overview of feminizing hormone therapy Primary author: General effects include breast development usually to Tanner stage 2 or 3 , a redistribution of facial and body subcutaneous fat, reduction of muscle mass, reduction of body hair and to a lesser extent, facial hair , change in sweat and odor patterns, and arrest and possible reversal of scalp hair loss. Sexual and gonadal effects include reduction in erectile function, changes in libido, reduced or absent sperm count and ejaculatory fluid, and reduced testicular size. Feminizing hormone therapy also brings about changes in emotional and social functioning. The general approach of therapy is to combine an estrogen with an androgen blocker, and in some cases a progestagen. Estrogens The primary class of estrogen used for feminizing therapy is beta estradiol, which is a "bioidentical" hormone in that it is chemically identical to that from a human ovary. The general approach is similar to estrogen replacement in agonadal i. No outcome studies have been conducted on injectable estradiol valerate or cypionate, presumably due to their uncommon modern use outside of transgender care settings; due to this limited use manufacturers have little incentive to produce this medicine, and shortages have been reported. Other delivery routes for estradiol such as transdermal gel or spray are formulated for the treatment of menopausal vasomotor symptoms and while convenient and effective in some transgender women, in others these routes may not be able to achieve blood levels in the physiologic female range. Compounded topical creams and gels also exist from specialty pharmacies; if these are to be used it is recommended that the prescriber consult with the compounding pharmacist to understand the specific details and dosing of the individual preparation. Compounded estradiol valerate or cypionate for injection also exists, and may be an alternative in times of shortage or more cost effective for those who must pay cash for their prescriptions. Ethical concerns have been raised regarding the methods of production of equine estrogens. Ethinyl estradiol is a synthetic estrogen used in contraceptive preparations and is associated with an increased thrombotic risk. Side effects of estrogens may include migraines, mood swings, hot flashes, and weight gain. Unfortunately many of these characteristics are permanent upon completion of natal puberty and are irreversible. Androgen blockers allow the use of lower estradiol dosing, in contrast to the supraphysiologic estrogen levels and associated risks previously used to affect pituitary gonadotropin suppression. Spironolactone is a potassium sparing diuretic, which in higher doses also has direct anti-androgen receptor activity as well as a suppressive effect on testosterone synthesis. Due to its diuretic effect, patients may experience self-limited polyuria, polydipsia, or orthostasis. Finasteride blocks 5-alpha reductase type 2 and 3 mediated conversion of testosterone to the potent androgen dihydrotestosterone. Since these medications block neither the production nor action of testosterone, their antiandrogen effect is less than that encountered with full blockade. Antiandrogens - other approaches Antiandrogens can also be used alone to bring reduced masculinization and minimal breast development, or in those patients who wish to first explore reduced testosterone levels alone, or in those with contraindications to estrogen therapy. In the absence of estrogen replacement, some patients may have unpleasant symptoms of hot flashes and low mood or energy. Long term full androgen blockade without hormone replacement in men who have undergone treatment for prostate cancer results in bone loss, and this effect would also be expected to occur in transgender individuals. Cyproterone has been associated with uncommon episodes of fulminant hepatitis. In some patients, complete androgen blockade may be difficult or even impossible using standard regimens. In cases of persistent elevations of testosterone in the setting of maximal antiandrogen dosing with good medication adherance, autonomous endogenous production i. An evaluation for testicular neoplasms should be performed with a scrotal exam as well as testing for elevated serum human chorianogonadotropin hCG , lactate dehydrogenase LDH , alpha-fetoprotein AFP levels, and possibly scrotal imaging. GnRH analogs are used routinely in the care of peripubertal transgender youth who require pubertal delay, and have been described in the care of transgender adults as well. Orchiectomy may represent an ideal option in transgender women who do not desire to retain their gonads; this brief, inexpensive, outpatient procedure requires only several days for recovery and does not preclude future vaginoplasty. There have been no well-designed studies of the role of progestagens in feminizing hormone regimens. In reality some patients may respond favorably to progestagens while others may find negative effects on mood. While progestagens have some anti-androgen effect through central blockade of gonadotropins, there is also a theoretical risk of a direct androgenizing effect of progestagens. This class includes micronized bioidentical progesterone Prometrium as well as a number of synthetic progestins. The most commonly used synthetic progestin in the context of transgender care is the oral medroxyprogesterone acetate Provera. While concerns exist from the Women's Health Initiative WHI regarding risks of cardiovascular disease and breast cancer in the setting of medroxyprogesterone use, these concerns likely do not apply in the context of transgender care for several reasons. First, the transgender women may be at lower risk of breast cancer than non-transgender women. Second, this arm of the WHI involved the use of conjugated equine estrogens in combination with medroxyprogesterone in a sample of menopausal women, some of whom were as long as 10 years post-menopausal at the time of hormone initiation. Third, while statistically significant, the clinical significance of the findings in the WHI was subtle at best. The study aimed to evaluate the role of menopausal hormone therapy in the prevention of chronic disease. The actual findings in the conjugated equine estrogen plus medroxyprogesterone group were an excess absolute risk per 10 person-years of 7 more cardiac events events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers, with no change in overall mortality. In the setting of gender affirming care, there are numerous differences to the findings of the WHI: Considering these differences in demographics and goals of therapy, extremely modest increase in overall risk, and lack of difference in mortality, as well as more recent reassuring data with other forms of estrogen, the risks of using progestagens in transgender women are likely minimal or even absent Grading: Other synthetic progestins may be used as necessitated by formulary limitations; some evidence suggests that norpregnane derived progestins norethindrone, norgestrel may have an increased risk of venous thromboembolism. Hormone preparations and dosing Grading: T O M Hormone.
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