Plasma protein changes induced by two orally administered androgen derivatives.

Epostane is a synthetic 17 alpha-alkylated 5 beta-androstane derivative, active following oral administration and devoid of any apparent androgenic, estrogenic or antiestrogenic potency. Circulating concentrations of 13 different plasma proteins were measured in eight women before and after 2 and 4 weeks of daily oral intake of 600 mg of epostane. The results were compared with those previously found during administration of the same daily dose of danazol, a synthetic 17 alpha-alkylated androgen derivative with known androgenic/anabolic activity. Epostane significantly suppressed serum levels of sex hormone-binding globulin, pregnancy zone protein and thyroxin-binding globulin and increased the levels of transthyretin. Haptoglobins, plasminogen and transferrin showed minor and/or transient changes and the levels of high density lipoproteins, alpha2-macroglobulin, albumin, C1-esterase inactivator, C3 complement and transcortin remained unaffected. The pattern of changes in plasma proteins was almost identical to that induced by administration of danazol, although the effects of epostane were somewhat weaker. Thus epostane is capable of inducing substantial changes in the pattern of steroid-sensitive plasma proteins in an androgen-like fashion despite its apparent lack of androgenic activity. The capacity of a steroid to induce such changes thus seems to be tied to the chemical structure rather than to the intrinsic hormonal activity of the molecule.

Relationship between serum testosterone and sex hormone binding globulin in menstruating and postmenopausal women.

The relationship between total testosterone (T), sex hormone binding globulin (SHBG) and calculated non-SHBG-bound testosterone (NST) was studied in randomly collected blood samples from healthy menstruating (n = 61) and postmenopausal (n = 65) women. In 12 of the menstruating women, blood samples were also collected more frequently during the menstrual cycle. Total T and SHBG were positively correlated in menstruating women in random samples as well as during different phases of the menstrual cycle, but not in postmenopausal women. Upper and lower limits of NST were independent of SHBG in menstruating but not in postmenopausal women. The data are at variance with the common concept about SHBG regulation and suggest a kind of compensatory mechanism in order to maintain a constant androgen homeostasis in menstruating but not in postmenopausal women. Consequently, supranormal total T or subnormal SHBG values do not necessarily indicate hyperandrogenicity in normally menstruating women.

Decreasing serum levels of sex hormone-binding globulin around the menopause and temporary relation to changing levels of ovarian steroids, as demonstrated in a longitudinal study.

Blood samples collected longitudinally in 17 women over a period of 3 years, starting 11/2 years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17 beta-estradiol (E2), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 +/- 1.67 (standard deviation) mg/l to 3.95 +/- 1.61 mg/l was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant (P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 +/- 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% (P less than 0.001). Of the hormones, only E2 exhibited a marked decrease (P less than 0.01) within this same 6-month period. The changes in SHBG during the 6-month transition period from premenopause to postmenopause correlated significantly (P = 0.013) only with those of E2. It is concluded that decreasing E2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause.

Epostane in nonpregnant females: effects on progesterone, 17 alpha-hydroxyprogesterone, and 17 beta-estradiol of two dose levels given for one month.

So far, the use of epostane, a relatively new inhibitor of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase enzyme system (3 beta-HSD), has been confined to short-term interference with luteal and placental function. This study explored whether epostane treatment from the beginning of the cycle for approximately 1 month would also inhibit ovarian follicular function. Twenty females with regular cycles received epostane 150 mg/day (ten healthy volunteers) or 600 mg/day (ten patients with endometriosis). Blood samples were drawn three times per week during control and treatment cycles. At 150 mg/day the mean total area under the serum concentration curve (AUC) of estradiol (E2) was somewhat higher than during the control cycles, despite apparently lower preovulatory E2 surges. During medication the highest value of E2 was found during the luteal phase. The mean AUC of progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) during the luteal surge was decreased by approximately 45% each. At 600 mg/day all evaluable patients had lower AUC of E2 than during the control cycle. The mean decrease in AUC of P and 17-OHP was much more pronounced than in the lower dose group. Six of the ten patients showed no hormonal signs of follicular development and, consequently, anovulation. The capacity of epostane to modulate or inhibit, depending on the dose, ovarian follicular steroidogenesis and ovulation may prove valuable in a variety of clinical conditions.