The effects of prolonged hypertestosteronemia on adrenocortical biosynthesis in oophorectomized women.
Adrenal androgen production and adrenocortical biosynthesis are frequently abnormal in women with hyperandrogenism. It is possible that these abnormalities result from hypertestosteronemia of ovarian origin. We prospectively studied the effect of prolonged testosterone (T) administration on adrenocortical biosynthesis and basal hormone levels in seven oophorectomized euandrogenic volunteers, who received 20 mg T in oil (USP), im, three times weekly for 3 weeks. Blood was sampled before T administration (week 0), during therapy (weeks 1, 2, and 3), and 1 week after discontinuation of the medication (week 4). Acute adrenal stimulation using 250 micrograms ACTH-(1-24), iv, was performed on weeks 0, 2, and 3. Circulating T rose from an average of 1.53 nmol/L to 27.9 nmol/L by the end of week 3. Both LH and FSH decreased with T administration, while PRL rose slightly during the initial weeks of T therapy. Little change was observed in the basal levels of 17-hydroxyprogesterone, 11-deoxycortisol, 17-hydroxypregnenolone, estrone, and estradiol. Androstenedione (A) rose concurrent with T administration and normalized after therapy discontinuation. Dehydroepiandrosterone (DHA) decreased significantly with T administration, while DHA sulfate (DHS) increased, leading to an increased DHS/DHA ratio. Total cortisol (F) decreased during T therapy; however, corticosteroid-binding globulin levels also decreased, and the unbound F level remained unchanged. No significant change in adrenocortical response (measured by either the absolute poststimulation level or the net increment in steroid levels) for any steroid was noted after T administration. Although the absolute poststimulation level of A was higher during T administration, this change reflected the increased basal A levels, since the increment in A from 0-60 min was not different. In conclusion, raising endogenous T levels in oophorectomized healthy women 10- to 15-fold for a period of 3 weeks produced a decrease in circulating total F and corticosteroid-binding globulin levels, while maintaining normal levels of unbound F. Although the very high T levels produced in this study resulted in an increased DHS/DHA serum ratio, it remains to be proven that the lesser degree of hypertestosteronemia usually observed in hyperandrogenic patients is sufficient to alter DHS metabolism. With this exception, the adrenocortical biosynthetic abnormalities frequently noted in hyperandrogenism do not appear to result from the elevated circulating T levels.
Azziz
R
R
Department of Obstetrics and Gynecology, University of Alabama, Birmingham 35294.
Gay
F L
FL
Potter
S R
SR
Bradley
E
E
Boots
L R
LR
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000735:Androstenedione / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005916:Globulins / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D010052:Ovariectomy; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D005916:Globulins; D006908:Hydroxyprogesterones; D004970:Estrone; D006907:17-alpha-Hydroxypregnenolone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003350:Cortodoxone; D006854:Hydrocortisone