Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome.

OBJECTIVE: To compare androgen responses during ACTH infusion among women with polycystic ovary syndrome (PCOS) and healthy women. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Women with PCOS (n = 13) and healthy controls (n = 15). INTERVENTION(S): Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. MAIN OUTCOME MEASURE(S): Comparison of basal and stimulated levels of 17α-hydroxyprogesterone (17-OHP), androgens, and cortisol (F) during ACTH infusion with those after hCG injection within individual subjects. RESULT(S): In women with PCOS increased 17-OHP, androstenedione (A), and DHEA responses during ACTH infusion were comparable to those observed in healthy controls. The magnitude of responses was highly variable among women with PCOS. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in women with PCOS and healthy controls. CONCLUSION(S): Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. CLINICAL TRIAL REGISTRATION NUMBER: NCT00747617.

Lack of Serum anti-Mullerian hormone responses after recombinant human chorionic gonadotropin stimulation in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is an anovulatory disorder characterized by excess androgen production and increased LH secretion. Serum anti-Mullerian hormone (AMH) is also elevated in this disorder. Women with PCOS exhibit a positive correlation between AMH and LH levels and recent in vitro data demonstrate that LH can directly stimulate AMH production by granulosa cells from women with PCOS. OBJECTIVE: The objective of the study was to directly test whether LH increases AMH production in women with PCOS in vivo by assessing responses after recombinant human chorionic gonadotropin (r-hCG) stimulation. DESIGN: This was a prospective study. SETTING: The study was conducted at a research center at an academic medical center. PARTICIPANTS: Women with PCOS (n = 28) and normal controls (n = 29) participated in the study. INTERVENTIONS: Blood samples were obtained before and 24 hours after iv administration of 25 µg r-hCG. MAIN OUTCOME MEASURES: Basal and stimulated serum AMH, androstenedione, T, and 17-hydroxyprogesterone levels were measured. RESULTS: Baseline AMH levels in women with PCOS were greater than in normal controls and correlated with levels of LH as well as androstenedione, T, and 17-hydroxyprogesterone. A rise of serum AMH levels was not observed after r-hCG administration in women with PCOS or normal ovaries. CONCLUSION: These findings are in contrast to in vitro evidence demonstrating that AMH secretion by granulosa cells of PCOS women in response to LH stimulation and suggest AMH regulation in vivo is complex and that the elevated serum AMH in women with PCOS is not a direct effect of the excess LH production characteristic of PCOS.

Relationship between 17-hydroxyprogesterone responses to human chorionic gonadotropin and markers of ovarian follicle morphology in women with polycystic ovary syndrome.

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.

Decreased inhibin B responses following recombinant human chorionic gonadotropin administration in normal women and women with polycystic ovary syndrome.

OBJECTIVE: To determine whether granulosa cells contribute to excess androgen production, by assessing inhibin B (Inh B) responses to hCG in women with polycystic ovary syndrome (PCOS) and in normal women. DESIGN: Prospective study. SETTING: Academic medical center. PATIENT(S): Twenty women with PCOS and 16 normal women. INTERVENTION(S): Blood samples obtained before and 24 hours after injection of 25 µg recombinant hCG (r-hCG). MAIN OUTCOME MEASURE(S): Basal and stimulated Inh B, E2, androstenedione (A), and T responses after r-hCG administration. RESULT(S): In normal and PCOS women, r-hCG induced a significant reduction of Inh B levels. Lowered Inh B responses were not related to body mass index, PCOS status, or age by multivariate regression. Recombinant hCG significantly increased serum A and E2 in both normal and PCOS women. CONCLUSION(S): In normal and PCOS women, Inh B production was decreased following r-hCG administration. These findings strongly suggest that in PCOS women androgen excess is not enhanced by LH-stimulated Inh B production. CLINICAL TRIAL REGISTRATION NUMBER: NCT00747617.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

OBJECTIVE: To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). DESIGN: Cohort SETTING: Academic assisted reproduction center. PATIENT(S): Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval MAIN OUTCOME MEASURE(S): Ongoing pregnancy beyond 9 weeks of gestation. RESULT(S): Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. CONCLUSION(S): In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies.

Polycystic ovary syndrome and acne.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.

Serum anti-mullerian hormone concentrations are elevated in oligomenorrheic girls without evidence of hyperandrogenism.

CONTEXT: Serum anti-Müllerian hormone (AMH) levels are significantly elevated in adolescents with polycystic ovary syndrome (PCOS) compared to normal controls. Whether adolescents with oligomenorrhea have elevated AMH levels is unknown. OBJECTIVE: This study was performed to assess serum AMH levels in oligomenorrheic (OLIGO) girls without evidence of hyperandrogenism. DESIGN: This was a prospective study comparing AMH levels in OLIGO, PCOS, and normal control adolescents. SETTING: The study was conducted through four tertiary academic medical centers. PARTICIPANTS: The study groups were comprised of OLIGO (n = 24), PCOS (n = 153), and normal adolescent girls (n = 39), as well as PCOS (n = 73) and normal adult women (n = 36). INTERVENTIONS: In each subject, serum AMH levels were assessed in the early to midfollicular phases for regularly menstruating subjects and on an arbitrary day for OLIGO or PCOS subjects. MAIN OUTCOME MEASURE(S): Basal serum AMH levels were assessed among OLIGO, PCOS, and normal girls, in addition to PCOS and normal women. RESULTS: OLIGO girls had serum AMH levels (5.33 +/- 0.47 ng/ml) that were significantly greater than the normal adolescents (3.05 +/- 0.31 ng/ml) and adults (2.33 +/- 0.22 ng/ml), but similar to values seen in the PCOS adolescents (5.28 +/- 0.26 ng/ml) and adults (6.36 +/- 0.47 ng/ml). Obese adolescents and PCOS women had significantly lower AMH levels compared to lean controls (P < 0.02). CONCLUSION: In OLIGO adolescents, elevated serum AMH levels suggest increased antral follicle number similar to that observed in girls with PCOS.