The Effects of Long Term Testosterone Administration on Pulsatile Luteinizing Hormone Secretion and on Ovarian Histology in Eugonadal Female to Male Transsexual Subjects

Abstract

Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9-36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD. Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02). Pulsatile LH secretion before and during T treatment was studied in five subjects. Neither the mean nadir LH interval nor the LH pulse amplitude changed significantly in these five subjects. The serum T level in the woman with the androgen-secreting ovarian tumor was 9.6 nmol/L, and it declined to normal after removal of the tumor. Her mean serum LH and FSH levels, the mean nadir LH interval, and LH pulse amplitude were in the normal range before and after removal of the tumor. Studies of ovarian histopathology in 26 transsexual subjects after long term androgen treatment revealed multiple cystic follicles in 18 subjects (69.2%), diffuse ovarian stromal hyperplasia in 21 subjects (80.8%), collagenization of the tunica albuginea in 25 subjects (96.2%), and luteinization of stromal cells in 7 subjects (26.9%). Findings consistent with criteria for the pathological diagnosis of polycystic ovaries, that is 3 of the 4 findings listed above, were present in 18 of the 26 subjects (69.2%).(ABSTRACT TRUNCATED AT 400 WORDS)

Safety aspects of 36 months of administration of long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals

“…With this treatment modality, serum testosterone levels, measured cross-sectionally, were 10.3G4.1 ng/ml (meanGS.D. ), which is largely supraphysiological (13,14). The wide range of plasma testosterone in these subjects is the result of the pharmacokinetic profile of the conventional testosterone esters, with serum testosterone levels varying from subnormal to supranormal (15).…”

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome

“…Pathological conditions in humans that cause hyperandrogenism, for example, congenital adrenal hyperplasia (38) and studies in transsexual women treated with high doses of testosterone (39,40,41,42) show conflicting outcomes.…”

The primary health care of transgender adults

“…13 Oestrogen levels fall only moderately among transmen on testosterone therapy, and their levels exceed those seen in postmenopausal women. 50 Reductions in sex hormone-binding globulin may further increase the concentration of free oestrogen. Progestogens are not routinely used in this population, 10 theoretically creating a scenario of unopposed oestrogen with an intact uterus.…”