scholarly journals Comparison of Follicle-Stimulating-Hormone-Stimulated Dimeric Inhibin and Estradiol Responses as Indicators of Granulosa Cell Function in Polycystic Ovary Syndrome and Normal Women

2006 ◽  
Vol 91 (8) ◽  
pp. 2920-2925 ◽  
Author(s):  
Deborah S. Wachs ◽  
Mickey S. Coffler ◽  
Pamela J. Malcom ◽  
R. Jeffrey Chang

Abstract Context: Follicular phase secretion of inhibin B, like that of estradiol (E2), correlates with the quantity and quality of developing follicles. However, it has not been established whether inhibin B responses to gonadotropin stimulation parallel those of E2 as a reflection of granulosa cell functional capacity. Objective: Our objective was to determine whether inhibin B responses to FSH stimulation are similar to those of E2 in women with polycystic ovary syndrome (PCOS) and normal women. Design and Setting: We conducted a prospective study to compare ovarian responses in two groups of women at a general clinical research center in a tertiary academic medical center. Patients: Women with PCOS, 18–35 yr (n = 19), and normal ovulatory controls, 18–35 yr (n = 7), were recruited for study. Interventions: Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH, 150 IU. Main Outcome Measures: Serum E2, inhibin A, and inhibin B responses after FSH administration were assessed. Results: In PCOS women, the 24-h production of inhibin B and E2 after FSH was significantly greater than that of normal controls. Within the PCOS group, the fold change in inhibin B was significantly greater than that of E2. Inhibin A responses between groups were similar and of markedly lower magnitude. Conclusions: FSH-stimulated inhibin B responses may be employed to assess the functional capacity of granulosa cells in PCOS and normal women.

2009 ◽  
Vol 25 (1) ◽  
pp. 198-203 ◽  
Author(s):  
M. A. Rosencrantz ◽  
D. S. Wachs ◽  
M. S. Coffler ◽  
P. J. Malcom ◽  
M. Donohue ◽  
...  

2006 ◽  
Vol 91 (9) ◽  
pp. 3503-3506 ◽  
Author(s):  
Rinku V. Mehta ◽  
Pamela J. Malcom ◽  
R. Jeffrey Chang

Abstract 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. 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. Design: We conducted a prospective cohort study. Subjects and Setting: We studied 11 women with PCOS at an institutional general clinical research center. 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. Main Outcome Measures: Baseline and stimulated E2 levels before and after treatment were assayed. 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. Conclusion: These findings indicate that in women with PCOS, the E2 hyperresponsiveness to FSH may not be attributable to increased circulating androgens.


2005 ◽  
Vol 20 (6) ◽  
pp. 322-326 ◽  
Author(s):  
Mustafa Torgac ◽  
Arif Kokcu ◽  
Mehmet B Cetinkaya ◽  
Tayfun Alper ◽  
Erdal Malatyalioglu

2014 ◽  
Vol 101 (1) ◽  
pp. 275-279 ◽  
Author(s):  
Rana F. Shayya ◽  
Marcus A. Rosencrantz ◽  
Sandy S. Chuan ◽  
Heidi Cook-Andersen ◽  
William E. Roudebush ◽  
...  

2015 ◽  
Vol 100 (1) ◽  
pp. 293-300 ◽  
Author(s):  
Kevin H. Maas ◽  
Sandy S. Chuan ◽  
Heidi Cook-Andersen ◽  
H. Irene Su ◽  
A. Duleba ◽  
...  

Abstract Context: Women with polycystic ovary syndrome (PCOS) have increased 17-hydroxyprogesterone (17-OHP) responses to gonadotropin stimulation although individual variability is substantial, as reflected by exaggerated as well as normal responses. The relationship between 17-OHP responses to gonadotropin stimulation and markers of ovarian function has not been assessed. Objective: To determine whether 17-OHP responses are associated with antral follicle count (AFC), anti-Mullerian hormone (AMH), or inhibin B (Inh B) levels in PCOS and normal women. Design: Prospective study. Setting: Research center at an academic medical center. Participants: Women with PCOS (n = 18) and normal controls (n = 18). Interventions: Blood samples were obtained before and 24 hours after administration of 25 μg recombinant-human chorionic gonadotropin. Ovarian imaging was conducted with three-dimensional pelvic ultrasound. Main Outcome Measures: Basal and stimulated levels of 17-OHP, androgens, estrogen, AMH, Inh B, and AFC. Results: In women with PCOS, 17-OHP responses were heterogeneous and inversely correlated with AMH and Inh B levels, but not AFC. In a subgroup of PCOS women with exaggerated 17-OHP responses, AMH levels were equivalent to that of normal women. In PCOS women with normal 17-OHP responses, AMH levels were markedly elevated. Conclusion: Based on heterogeneous 17-OHP responses to human chorionic gonadotropin in women with PCOS, AMH levels are inversely linked to ovarian androgen production while positively correlated with AFC. These findings suggest that in PCOS, AMH production may reflect redistribution of the follicle population or regulation by intraovarian mechanisms.


2008 ◽  
Vol 93 (5) ◽  
pp. 1827-1833 ◽  
Author(s):  
Deborah S. Wachs ◽  
Mickey S. Coffler ◽  
Pamela J. Malcom ◽  
Shunichi Shimasaki ◽  
R. Jeffrey Chang

Abstract Context: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. Objective: The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. Design: A prospective study was conducted to compare androgen production in response to FSH in two groups of women. Setting: The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Patients: Women with PCOS, 18–35 yr (n = 20), and normal ovulatory controls, 18–35 yr (n = 10), were recruited for study. Interventions: Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). Main Outcome Measures: The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Results: Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. Conclusions: These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.


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