Effects of Long-Term Testosterone Administration on Gonadotropin Secretion in Agonadal Female to Male Transsexuals Compared with Hypogonadal and Normal Women*

Abstract

We investigated the effects of long term testosterone (T) administration on pulsatile gonadotropin secretion in agonadal women and the effects of estradiol (E2) on gonadotropin secretion in eugonadal women in the follicular phase of the menstrual cycle. We studied 4 groups: A) 28 eugonadal women in the early follicular phase of the menstrual cycle, B) 11 hypogonadal women, C) 13 agonadal female to male (f-t-m) transsexuals treated for at least 3 months with 120-160 mg T undecanoate (TU)/day, orally, and D) 5 agonadal f-to-m transsexuals treated for at least 6 months with 250 mg of a mixture of testosterone esters, im (im T-esters), every 2 weeks. The eugonadal women in the early follicular phase had a mean serum E2 level of 193 +/- 94 (+/- SD) pmol/L, significantly higher (P less than 0.01) than that in the hypogonadal women (60 +/- 24 pmol/L), whereas there was no difference in the mean serum T levels (1.8 +/- 0.7 vs. 2.3 +/- 1.5 nmol/L). the higher serum E2 level in the eugonadal women was associated with a significantly lower mean serum LH level (6.9 +/- 2.6 vs. 44.6 +/- 17.6 U/L; P less than 0.01) and LH pulse amplitude (2.8 +/- 1.0 vs. 12.6 +/- 4.8 U/L; P less than 0.01), whereas the mean nadir LH interval did not differ between the two groups (75 +/- 29 vs. 81 +/- 49 min). The mean serum T level in the agonadal f-to-m transsexuals treated with oral TU was significantly higher (P less than 0.01) than that in the hypogonadal women (9.7 +/- 4.7 vs. 2.3 +/- 1.5 nmol/L). In spite of this elevated T level there was no difference in the mean serum LH level (38.4 +/- 14.7 vs. 44.6 +/- 17.6 U/L), LH pulse amplitude (14.3 +/- 5.7 vs. 12.6 +/- 4.8 U/L), or nadir LH interval (72 +/- 27 vs. 81 +/- 49 min) in these groups. Also, the mean serum E2 (64 +/- 16 vs. 60 +/- 24 pmol/L and FSH levels (62 +/- 17 vs. 64 +/- 28 U/L) did not differ between these groups. Treatment of the agonadal f-to-m transsexuals with im T-esters resulted in mean serum T and E2 levels of 34.4 +/- 27.0 nmol/L and 121 +/- 54 pmol/L, respectively, both significantly higher (P less than 0.01) than those in groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)

Menstrual Abnormalities in Women with Cushing’s Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels

“…However, these alterations have only been produced when serum levels of testosterone are elevated, higher than the levels encountered in normal males, females with virilizing tumors, or the patients studied here (53)(54)(55)(56). Administration of testosterone to women at doses that raised serum levels of testosterone to those seen in normal men does not alter serum gonadotropin levels or LH pulsatility or result in menstrual cycle regularity (57,58). Further evidence for the minor role of androgens in the regulation of gonadotropin secretion comes from the observation in a man with estrogen resistance secondary to a mutation of the estrogen receptor that despite normal circulating androgen levels his serum gonadotropin levels were elevated, indicating the main feedback mechanism to be via estrogens rather than androgens (59).…”

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).…”

Endocrine Treatment of Transsexual People: A Review of Treatment Regimens, Outcomes, and Adverse Effects

“…Injectable testosterone was often used alone, both before and after oophorectomy (Table 1). Oral testosterone undecanoate, available outside of the United States, has been associated with more consistent but lower serum testosterone levels (49). It may not adequately suppress menstruation without the addition of a progestin (12,20).…”