The effect of androgen blockade on granulosa cell estradiol production after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome.
BACKGROUND
Previously, we have shown that women with polycystic ovary syndrome (PCOS) exhibit an exaggerated serum estradiol (E(2)) response to recombinant human FSH (rhFSH) (150 IU) compared with similarly treated normal women. This enhanced granulosa cell responsiveness is consistent with excessive follicular development after gonadotropin therapy and the corresponding risk of ovarian hyperstimulation syndrome. In vitro studies have shown that granulosa cells treated with androgens display greater FSH-induced E(2) production than untreated cells, suggesting a role for androgens in granulosa cell responsiveness.


OBJECTIVE
This study was conducted to determine whether blockade of androgen action in PCOS women by administration of the antiandrogen flutamide would alter E(2) responses to rhFSH.


METHODS
We conducted a prospective cohort study.


METHODS
We studied 11 women with PCOS at an institutional general clinical research center.


METHODS
On study d 1, each subject received 150 IU rhFSH iv. Frequent blood samples were obtained over 24 h. After completion of rhFSH stimulation, each subject was treated with flutamide, 125 mg, twice daily, for 6 wk. Thereafter, the rhFSH stimulation test was repeated.


METHODS
Baseline and stimulated E(2) levels before and after treatment were assayed.


RESULTS
Mean baseline and maximally stimulated E(2), integrated E(2) response, and fold change in E(2) were not different before and after treatment. Levels of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, estrone, and SHBG before and after treatment were unchanged. Baseline dehydroepiandrosterone sulfate levels declined significantly after flutamide therapy.


CONCLUSIONS
These findings indicate that in women with PCOS, the E(2) hyperresponsiveness to FSH may not be attributable to increased circulating androgens.
Mehta
Rinku V
RV
Department of Reproductive Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0633, USA.
Malcom
Pamela J
PJ
Chang
R Jeffrey
RJ
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology*; D000735:Androstenedione / Q000097:blood; D019540:Area Under Curve; D015331:Cohort Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000096:biosynthesis* / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D011994:Recombinant Proteins; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D005485:Flutamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone