{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:27:38Z","timestamp":1758126458456},"reference-count":21,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Previously, we have shown that women with polycystic ovary syndrome (PCOS) exhibit an exaggerated serum estradiol (E2) 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 E2 production than untreated cells, suggesting a role for androgens in granulosa cell responsiveness.<\/jats:p><jats:p>Main Objective: This study was conducted to determine whether blockade of androgen action in PCOS women by administration of the antiandrogen flutamide would alter E2 responses to rhFSH.<\/jats:p><jats:p>Design: We conducted a prospective cohort study.<\/jats:p><jats:p>Subjects and Setting: We studied 11 women with PCOS at an institutional general clinical research center.<\/jats:p><jats:p>Intervention: 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.<\/jats:p><jats:p>Main Outcome Measures: Baseline and stimulated E2 levels before and after treatment were assayed.<\/jats:p><jats:p>Results: Mean baseline and maximally stimulated E2, integrated E2 response, and fold change in E2 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.<\/jats:p><jats:p>Conclusion: These findings indicate that in women with PCOS, the E2 hyperresponsiveness to FSH may not be attributable to increased circulating androgens.<\/jats:p>","DOI":"10.1210\/jc.2006-0752","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T01:38:01Z","timestamp":1151458681000},"page":"3503-3506","source":"Crossref","is-referenced-by-count":8,"title":["The Effect of Androgen Blockade on Granulosa Cell Estradiol Production after Follicle-Stimulating Hormone Stimulation in Women with Polycystic Ovary Syndrome"],"prefix":"10.1210","volume":"91","author":[{"given":"Rinku V.","family":"Mehta","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"Malcom","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Jeffrey","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613392375000_R1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/oxfordjournals.humrep.a137638","article-title":"Granulosa cells of polycystic ovaries: are they normal or abnormal?","volume":"7","author":"Erickson","year":"1992","journal-title":"Hum Reprod"},{"key":"2020071613392375000_R2","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1210\/jc.2002-021280","article-title":"Evidence for abnormal granulosa cell responsiveness to follicle-stimulating hormone in women with polycystic ovary syndrome","volume":"88","author":"Coffler","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613392375000_R3","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1046\/j.1365-2265.1996.724545.x","article-title":"Functional integrity of granulosa cells from polycystic ovaries","volume":"44","author":"Almahbobi","year":"1996","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613392375000_R4","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1210\/jcem.84.8.5929","article-title":"Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development","volume":"84","author":"Weil","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613392375000_R5","first-page":"2622","article-title":"Androgens stimulate early stages of follicular growth in the primate ovary","volume":"101","author":"Vendola","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613392375000_R6","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1210\/endo-109-4-1303","article-title":"Evidence that granulosa cell aromatase induction\/activation by follicle-stimulating hormone is an androgen receptor-regulated process in vitro","volume":"109","author":"Hillier","year":"1981","journal-title":"Endocrinology"},{"key":"2020071613392375000_R7","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1210\/endo-122-6-2780","article-title":"Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgen and the stage of follicular maturation","volume":"122","author":"Harlow","year":"1988","journal-title":"Endocrinology"},{"key":"2020071613392375000_R8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1210\/jcem-62-1-16","article-title":"Histopathological effects of exogenously administered testosterone in 19 female to male transsexuals","volume":"62","author":"Futterweit","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613392375000_R9","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1365-2559.1991.tb00235.x","article-title":"Ovarian morphology in long term androgen treated female to male transsexuals. A human model for the study of polycystic ovary syndrome?","volume":"19","author":"Pache","year":"1991","journal-title":"Histopathology"},{"key":"2020071613392375000_R10","first-page":"702","article-title":"Polycystic ovaries in female to male transsexuals","volume":"39","author":"Pache","year":"1993","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613392375000_R11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0303-7207(77)90091-0","article-title":"Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens","volume":"8","author":"Nimrod","year":"1977","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613392375000_R12","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1210\/endo-119-3-1403","article-title":"Androgen modulation of follicle-stimulating hormone-induced granulosa cell steroidogenesis in the primate ovary","volume":"119","author":"Harlow","year":"1986","journal-title":"Endocrinology"},{"key":"2020071613392375000_R13","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1210\/endo-107-4-1027","article-title":"Enhancement of follicle-stimulating hormone-induced aromatase activity by androgens in cultured rat granulosa cells","volume":"107","author":"Daniel","year":"1979","journal-title":"Endocrinology"},{"key":"2020071613392375000_R14","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1210\/endo-102-4-1275","article-title":"Stimulation of aromatase activity by follicle-stimulating hormone in rat granulosa cells in vivo and in vitro","volume":"102","author":"Erickson","year":"1978","journal-title":"Endocrinology"},{"key":"2020071613392375000_R15","first-page":"25","article-title":"Low-dose flutamide (125 mg\/day) as maintenance therapy in the treatment of hirsutism","volume":"56","author":"Venturoli","year":"2002","journal-title":"Horm Res"},{"key":"2020071613392375000_R16","first-page":"3251","article-title":"Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide","volume":"85","author":"Ibanez","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613392375000_R17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000077827","article-title":"Flutamide suppresses adrenal steroidogenesis but has no effect on insulin resistance and secretion and lipid levels in overweight women with polycystic ovary syndrome","volume":"58","author":"Vrbikova","year":"2004","journal-title":"Gynecol Obstet Invest"},{"key":"2020071613392375000_R18","doi-asserted-by":"crossref","first-page":"6077","DOI":"10.1016\/S0021-9258(20)65107-9","article-title":"Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells","volume":"257","author":"Adashi","year":"1982","journal-title":"J Biol Chem"},{"key":"2020071613392375000_R19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1210\/endo-115-1-41","article-title":"Estrogens enhance the adenosine 3\u2032,5\u2032-monophosphate-mediated induction of follicle-stimulating hormone and luteinizing hormone receptors in rat granulosa cells","volume":"115","author":"Knecht","year":"1984","journal-title":"Endocrinology"},{"key":"2020071613392375000_R20","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1093\/humrep\/dei004","article-title":"Absence of hepatotoxicity after long-term, low-dose flutamide in hyperandrogenic girls and young women","volume":"20","author":"Ibanez","year":"2005","journal-title":"Hum Reprod"},{"key":"2020071613392375000_R21","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.fertnstert.2004.08.020","article-title":"Abnormal aminotransferase activity in women with polycystic ovary syndrome","volume":"83","author":"Schwimmer","year":"2005","journal-title":"Fertil Steril"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/91\/9\/3503\/9063896\/jcem3503.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/91\/9\/3503\/9063896\/jcem3503.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T23:04:14Z","timestamp":1627513454000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/91\/9\/3503\/2656693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,1]]},"references-count":21,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2006,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2006-0752","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,1]]}}}