The Effect of Chronic and Acyclic Elevation of Circulating Androstenedione or Estrone Concentrations on Ovarian Function in the Rhesus Monkey*

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Abstract
The concept that chronically elevated blood androstenedione concentrations increase the incidence of anovulation in the primate and that acyclic elevated basal blood androgen and/or estrogen concentrations cause abnormal gonadotropin secretion was studied. Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing filled with androstenedione or estrone and compared with controls. Androstenedione implants increased the serum androstenedione concentrations from 1.6 ± 0.1 (se) ng/ml to 6.30 ± 0.27 ng/ml. By peripheral conversion the testosterone concentration increased from control values of 279 ± 10 (se) pg/ml to 1280 ± 41 pg/ml. The testosterone concentration in the estrone-treated monkeys was 247 ± 9.7 pg/ml. The estrone concentrations were: controls, 63.2 ± 3.1 (se) pg/ml; androstenedione-treated monkeys, 63.2 ±3.1 pg/ml; and estrone-treated animals, 150 ± 5.3 pg/ml. The corresponding estradiol concentrations were: control animals, 35.1 ± 2.1 (se) pg/ml; androstenedione animals, 30.9 ± 1.8 pg/ml; and estrone-treated monkeys, 65.7 ± 3.9 pg/ml. There was no difference in the morning serum cortisol concentrations between any of the three groups or between ovulatory or anovulatory months. The chronic elevation of either androstenedione or estrone caused an increased incidence of anovulation compared with the controls. Increased estrogen concentrations caused increased anovulation during both summer and winter months; however, increased androgen concentrations caused increased anovulation only during the summer months. However, LH concentrations were unaffected in either group but were lower during anovulation months in all three groups. An LH or FSH surge followed an estradiol bolus in three of four control animals and four of six androstenedione-treated but none of the estrone-treated monkeys. Histological examination of ovarian biopsies demonstrated thickening of the tunica albuginea ovarii in androgen-treated ovaries and an apparent increased number of atretic follicles. Corpora lutea were absent in the ovaries of the estrogen-treated monkeys, but otherwise these ovaries were similar to those of controls. It is concluded that chronic acyclic elevation of blood androstenedione (and resultant testosterone) increases seasonal anovulation in the rhesus monkey. Increased blood estrone (and resultant estradiol) leads to almost complete anovulation throughout the year and renders the central nervous systempituitary axis insensitive to positive feedback effect of estradiol. Neither treatment caused an increase in basal LH concentrations. We suggest that abnormal gonadotropin secretion in polycystic ovarian syndrome is not secondary to elevated acyclic basal levels of circulating androgen or estrogen. (Endocrinology 116:2209-2220,1985)