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Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Dr. Janet E. Hall, Reproductive Endocrine Unit, BHX-5, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: jehall{at}partners.org.
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Abstract |
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4A), SHBG, and dehydroepiandrosterone sulfate (DHEAS) were measured at baseline in the early follicular phase (EFP) in all subjects. LH, FSH, E2, and progesterone (P4) were then measured daily for a complete menstrual cycle in 16 women with normal ovarian morphology and in 26 women with PCOM. T, 4A, SHBG, and DHEAS levels were measured in pools of three daily samples in each of the EFP, midcycle, and midluteal phases. An additional 26 normal women (13 with normal ovarian morphology and 13 with PCOM) were studied in the EFP to assess pulsatile LH secretion, insulin and glucose levels, and the ovarian response to human chorionic gonadotropin. At baseline, there were no differences in body mass index or hirsutism scores between women with PCOM and normal ovaries. In daily samples across the menstrual cycle LH, FSH, E2, and P4 did not differ between women with PCOM and those with normal ovaries, and there was no difference in LH pulse amplitude or frequency in the EFP frequent sampling studies. In women with PCOM, T (P < 0.01), free T (P < 0.005), and DHEAS (P < 0.01) levels were higher at baseline in the EFP, and SHBG was lower (P < 0.05). Differences in 4A did not reach significance (P = 0.14). T, free T, 4A, and DHEAS were also increased in PCOM across the menstrual cycle (P < 0.05). In addition, 17-hydroxyprogesterone (P < 0.02), 4A (P < 0.01), and T (P < 0.01) responses to human chorionic gonadotropin were greater in women with PCOM. Fasting glucose was not different between the two groups, but fasting insulin was higher (P < 0.02) in PCOM women as was insulin resistance calculated from homeostatic model assessment (P < 0.01). These studies demonstrate that PCOM in nonhirsute women with documented ovulatory cycles is associated with normal E2, P4, and gonadotropin dynamics, but higher androgen and insulin levels and lower SHBG levels. Taken together, these findings suggest that PCOM with ovulatory cycles exists as a discrete entity, represents the mildest form of ovarian hyperandrogenism, and is associated with greater insulin resistance than in women with normal ovarian morphology. The absence of any neuroendocrine abnormality in women with PCOM and ovulatory cycles suggests that gonadotropin dysfunction is not required for increased androgen secretion, but may be critical for development of the anovulatory disorder associated with PCOS. |
Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Even more importantly, PCOM is also present in 16–25% of apparently normal women with regular cycles (16, 17, 18, 19). Although there are only a few studies that have attempted to characterize this group of women endocrinologically, some have suggested that PCOM in ovulatory women may be associated with some of the features commonly associated with PCOS, such as abnormal gonadotropin levels, lower levels of IGF-binding protein-1, increased insulin resistance and increased ovarian 17-hydroxyprogesterone (17OHP) and androgen responses to GnRH agonists (13, 19, 20, 21). However, results have not been consistent across studies. The lack of consistency in findings may relate to the small number of subjects studied, differences in subject characteristics, or differences in study design. In addition, no study has thoroughly investigated gonadotropin secretory dynamics. Thus, the significance of this morphology alone and its relation to PCOS is unclear.
The aim of the present study therefore was to determine whether abnormalities in gonadotropin and androgen secretion are present in women with proven ovulatory cycles and PCOM compared with those with normal ovarian morphology and to investigate the relationship of PCOM to measures of insulin resistance.
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Subjects and Methods |
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LH, FSH, E2, testosterone (T), androstenedione (4A), dehydroepiandrosterone sulfate (DHEAS), and SHBG were measured at baseline in the early follicular phase (EFP) using a pool of at least three samples. Ovarian morphology was objectively assessed by pelvic ultrasound. The majority of ultrasound examinations were performed transvaginally to optimize image quality. All ultrasound examinations were performed on the same machine (Sonolayer L, SAL-778 with a transvaginal 5-mHz probe, Toshiba, Japan) and interpreted by a single expert observer (J.M.A.). Assessment of polycystic morphology was based on a modification of the criteria of Adams et al. (8) and required eight or more cysts of 2–8 mm in diameter in a single plane with a peripheral distribution and the impression of increased stroma. Although the above constituted the primary criteria for assessment of PCOM, data were also analyzed using the newly described criteria from the Rotterdam Conference in which PCOM is defined by more than 12 follicles of 2–9 mm in diameter and/or an ovarian volume greater than 10 ml (23, 24).
LH, FSH, E2, and P4 were measured daily for a complete menstrual cycle in 16 women with normal ovarian morphology and in 26 women with PCOM. In addition to meeting the above criteria, all subjects provided clear documentation of the dates of menses from six previous cycles. The cycle of study was required to be 25–35 d in length and to have a luteal phase length of at least 10 d. The day of ovulation was identified from the serum values as previously described (25). Blood samples were pooled from three daily samples in the EFP (d 1–3 from the onset of menses), at midcycle (d –1, 0, and 1 in relation to the day of ovulation), and in the midluteal phase (d –1, 0, and 1 from the midpoint of the luteal phase) and assayed for T, 4A, DHEAS, and SHBG in subjects in whom sufficient sample was available (14 with normal ovaries and 19 with PCOM).
Twenty-six additional women (13 with normal ovaries and 13 with PCOM) meeting the criteria described above (including the requirement for an ovulatory progesterone level in the previous cycle) were studied in the follicular phase between d 1 and 7 from the onset of menses. Some of these subjects were included as normal controls in a previous report from this group (6). Subjects were admitted to the General Clinical Research Center in the morning after an overnight fast. Blood was sampled every 10 min for 8 h from 1600 h until midnight for assessment of pulsatile LH secretion, and subjects remained awake for the duration of frequent sampling. On the following morning, fasting samples were collected for glucose, insulin, DHEAS, T, 4A, and 17OHP measurements. Cholesterol and triglyceride levels were also measured in fasting samples. Human chorionic gonadotropin (hCG; 5000 IU) was administered im, and the subjects returned for an additional blood sample 24 h later.
Assays
LH, FSH, E2, P4, T, DHEAS, and 4A were assayed using methodologies that have been previously described (6, 26, 27, 28). T was measured by RIA after extraction, using highly specific antibodies generated by the Reproductive Endocrine Laboratory at Massachusetts General Hospital. The sensitivity of the assay was 5 ng/dl (0.2 nmol/liter), and both inter- and intraassay precisions were less than 10%. The upper limit of normal, defined as the mean ± 2 SD derived from a well characterized group of ovulatory women, is 111 ng/dl (3.9 nmol/liter). 4A was measured by direct RIA with interassay variabilities of 8.5% and 3% at low and high concentrations, respectively, and an upper limit of normal of 4.4 ng/ml (15.4 nmol/liter) in reproductive age women. LH was measured using a microparticle enzyme immunoassay (AxSYM, Abbott Laboratories, Chicago, IL). The intraassay coefficients of variation for LH were obtained from serum pools that were run at least 10 times throughout the assay in which the patient’s frequent sampling study was analyzed and were less than 5%. Results are reported in terms of the Second International Reference Preparation of human menopausal gonadotropin (WHO 71/223). SHBG was measured using a chemiluminescent enzyme immunometric assay (Immulite, Diagnostic Products Corp., Los Angeles, CA) with a reportable range of 2–180 nmol/liter and an interassay variability less than 8%. Insulin was measured by RIA as previously described (29). The lower limit of detection of the insulin assay was 1.0 µIU/ml.
Data analysis
Free T (FT) was calculated using total T and SHBG according to the formula validated by Vermeulen et al. (30). The ovaries were measured in three planes, and the volume was calculated by the formula for a prolate elipse (length x width x height x 0.5). Ultrasound volume is presented as the mean volume of both ovaries. If a dominant follicle larger than 10 mm was present, the contralateral ovary was used for calculation of ovarian volume. Analysis of pulsatile LH secretion was performed using a modification of the Santen and Bardin program that has previously been validated in GnRH-deficient subjects (31). Insulin resistance was calculated using the homeostasis model assessment (HOMA) method [HOMA-IR = glucose (mmol/liter) x insulin (IU/liter)/22.5] (32).
The Kolmogorov-Smirnov test was used to test for normality of distribution for all variables. The results of baseline testing, glucose, insulin, pulse analysis, and hCG testing were compared in women with and without PCOM using t tests or Mann-Whitney tests as appropriate. Linear and stepwise linear regressions were used to evaluate the influence of age on the relationship of DHEAS to PCOM. Linear regression was used to further examine the relationship of ovarian volume to hormonal measurements across all subjects. SHBG, T, 4A, and 17OHP levels after hCG administration were correlated with fasting insulin and HOMA.
For statistical analysis of the daily blood samples, the follicular and luteal phases were normalized to a 28-d cycle, as previously described (33), and a mean value was determined for each individual for the early (d –13 to –10), mid (d –9 to –6), and late (d –5 to –2) follicular phase; midcycle (d –1 to 1); and early (d 2–5), mid (d 6–9), and late (d 10–14) luteal phase of the cycle. Results were then compared between women with and without PCOM across cycle phases using repeated measures two-way ANOVA. T, SHBG, FT, 4A, and DHEAS from the EFP, midcycle, and midluteal phase were analyzed by repeated measures two-way ANOVA, followed by post hoc Newman-Keuls testing. P < 0.05 was considered significant unless otherwise indicated.
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Results |
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), although the PCOM group was slightly younger than those with normal ovaries. In women with PCOM, ovarian volume was twice that of women with normal ovaries (Table 1). Follicle number ranged from four to eight follicles per ovary in a single plane in women judged to have normal ovaries and from eight to 15 follicles per ovary in a peripheral distribution in a single plane in those with PCOM. EFP levels of T, FT, 4A, and DHEAS were higher in PCOM, and SHBG was lower (Table 1). Despite the absence of clinical signs of hyperandrogenism, T was above the normal range in four women with PCOM, but in none of those with normal ovaries. DHEAS was inversely related to age (r = 0.293; P < 0.03), but the difference in DHEAS between women with PCOM and those with normal ovarian morphology was independent of age. Across all subjects, ovarian volume was positively correlated with T (r = 0.44; P < 0.001) and 4A (r = 0.33; P < 0.02).
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). Although E2 levels appear to be slightly higher in the luteal phase in women with PCOM, this difference was not statistically significant when the data for each subject were normalized for cycle length.
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4A (P < 0.02) levels varied across the menstrual cycle, with the highest levels at midcycle, consistent with previous reports (34, 35). In addition, T levels were significantly higher in women with PCOM than in those with normal ovarian morphology (P < 0.03; Fig. 2), with the greatest differences apparent in the EFP and at midcycle (P < 0.05). 4A levels were also significantly different between the two groups of ovulatory women (P < 0.05), with the greatest difference seen in the EFP (P < 0.01). SHBG levels varied across the cycle (P < 0.01), a difference that was due primarily to slightly higher levels of SHBG in the luteal phase compared with midcycle in women with PCOM. SHBG levels tended to be lower in PCOM across the cycle, but differences did not reach statistical significance (P = 0.06; Fig. 2). FT followed the pattern of total T, with a significant effect of cycle phase (P < 0.001), and the highest levels occurred at midcycle in both groups. FT was higher in women with PCOM than in those with normal ovaries (P < 0.02; Fig. 2), a difference that was most pronounced in the EFP (P < 0.02) and at midcycle (P < 0.05). DHEAS levels did not change significantly across the cycle (Fig. 2), but they were higher in women with PCOM than in those with normal ovaries (P < 0.03).
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). In addition, there was no difference in either the amplitude or the frequency of pulsatile LH secretion between those with and without PCOM (Table 2).
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). There was an inverse relationship between SHBG and both fasting insulin (r = 0.406; P < 0.05) and HOMA (r = 0.413; P < 0.05). Systolic and diastolic blood pressures were not different between the two groups of ovulatory women (113.2 ± 3.4/72.8 ± 1.7 vs. 111.8 ± 2.7/69.8 ± 2.2 mm Hg in women with normal ovaries and PCOM). In addition, there was no significant difference in triglycerides (102.3 ± 14.0 vs. 86.4 ± 12.9 mg/dl), total cholesterol (155.5 ± 9.4 vs. 174.7 ± 8.9 mg/dl), low density lipoprotein (93.8 ± 7.5 vs. 106.0 ± 6.6 mg/dl), or high density lipoprotein (41.2 ± 2.6 vs. 48.8 ± 2.7 mg/dl) in women with normal ovaries and PCOM.
Twenty-four hours after the administration of hCG, 17OHP (P < 0.02), 4A (P < 0.01), and T (P < 0.01) levels were higher in PCOM (Fig. 3). Fasting insulin (r = 0.398; P = 0.05) and HOMA (r = 0.362; P = 0.08) tended to be positively correlated with 17OHP 24 h after hCG administration. Ovarian volume was significantly correlated with T (r = 0.51; P < 0.01), 4A (r = 0.50; P < 0.02), and 17OHP (r = 0.69; P < 0.001) 24 h after hCG administration and with fasting insulin (r = 0.43; P < 0.03) and HOMA (r = 0.42; P < 0.05). However, stepwise regression indicated that 17OHP was adequate for the prediction of ovarian volume, whereas the other variables did not add significant additional information.
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Discussion |
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Increased gonadotropin levels derived from single samples have been reported in women with PCOM and apparently normal cycles in some studies (16, 37), but were not seen in others in an apparently similar population (13, 19, 21). In the current study the presence of PCOM was not associated with any differences in LH or FSH measured in daily blood samples across the menstrual cycle, nor was it associated with the characteristic neuroendocrine abnormalities of increased LH pulse frequency and amplitude that are present in over 90% of women with PCOS (6, 38, 39). The differences in gonadotropin dynamics between ovulatory women with PCOM and patients with PCOS thus indicate that abnormalities in gonadotropin secretion are not required for, nor are they associated with, development of PCOM alone. This finding is supported by the identification of polycystic ovaries during normal childhood (9), when gonadotropin levels are low, and their occasional occurrence in patients with primary amenorrhea due to idiopathic hypogonadotropic hypogonadism, in whom gonadotropins are virtually absent (40).
In the absence of a difference in gonadotropin stimulation, T levels were higher in the presence of PCOM compared with normal morphology in the current studies, and both T and 4A were correlated with ovarian volume. Despite the absence of any clinical signs of hyperandrogenism, T levels were greater than 2 SD above the mean for normal women in four subjects with PCOM, but in none with normal ovarian morphology. The normal range for T in the assay used is somewhat higher than reported in other assays, but is based on a large group of well characterized women with regular cycles and no evidence of hyperandrogenism. The ovarian response to a GnRH agonist (41) and hCG (28) has been used to describe functional ovarian hyperandrogenism. In the current study, T, 4A, and 17-OHP responses to hCG were also higher in PCOM, although the response was considerably less than previously reported in patients with PCOS (28). A similar hyperresponsiveness to hCG in ovulatory women with polycystic ovaries was found in the studies by Gilling-Smith et al. (20) after GnRH agonist down-regulation, although the difference in response to GnRH agonist stimulation was not significant in the studies by Chang et al. (21). Several studies have recently addressed the difficulties in accurate measurement of T at the low levels present in normal women (42, 43). However, taken together, the baseline and stimulated androgen results in the current study suggest that PCOM in ovulatory women represents the mildest form of ovarian hyperandrogenism.
Recent studies in isolated thecal cells studied in vitro have provided evidence for a defect in steroidogenesis in women with PCOS compared with normal ovulatory controls (44). This defect in PCOS persists after many passages in culture (45), suggesting that it is independent of the in vivo hormonal milieu or that adaptive cellular changes occur after prolonged gonadotropin stimulation in vivo. Dysregulation of thecal cell androgen production appears to be an early manifestation of PCOS as adolescents with a history of premature pubarche who subsequently develop oligomenorrhea and hyperandrogenemia after menarche have an increased response of 17OHP to GnRH agonist (46). Other studies have suggested that a similar defect may also be present in vitro in thecal cells derived from ovulatory women with PCOM (44). The current studies in which androgen levels were higher in association with PCOM at baseline and in response to hCG in the absence of differences in gonadotropin levels are consistent with such an intrinsic ovarian mechanism.
The finding of increased DHEAS levels in the women with PCOM is of particular interest because the majority of evidence now indicates that the ovary is the primary source of androgen production in PCOS (47). However, increased adrenal androgen secretion is seen in a subset of patients with PCOS (48, 49, 50), and it has been suggested that adrenal hyperandrogenism may lead to the development of PCOS (51). The high prevalence of polycystic morphology and ovarian hyperandrogenism in patients with congenital adrenal hyperplasia supports a role for the adrenal in the development of PCOS. In addition, recent studies have shown that patients with premature pubarche, possibly secondary to exaggerated adrenarche, have a high prevalence of PCOM and are at significant risk for subsequent development of PCOS in adulthood (46, 52). However, the majority of adult women with PCOS do not have abnormalities in adrenal androgen secretion. This may imply that mechanisms other than adrenal hyperandrogenism are responsible for the development of PCOS in these women, but it may also suggest that other factors, such as hyperinsulinemia, may subsequently modify adrenal androgen secretion (53, 54).
Abnormalities in insulin signaling have been implicated in the pathogenesis of PCOS in a significant subset of affected patients (55). Although the role of hyperinsulinemia in the hyperandrogenism and ovulatory dysfunction of PCOS appears most prominent in obese patients (56), the response to insulin-sensitizing agents in lean PCOS patients (57) suggests that this mechanism may be operative across the broad spectrum of patients with PCOS. In the current studies, women with PCOM had higher fasting insulin levels and HOMA. Although still within the accepted normal range, these findings are consistent with a mild degree of insulin resistance, even in these otherwise asymptomatic women. The current results stand in contrast to earlier studies that reported normal fasting and glucose-stimulated insulin levels and normal insulin sensitivity in hyperandrogenemic women with regular menstrual cycles and PCOM (58). However, the results of the current study are supported by one previous study in which an increase in insulin resistance in nonhirsute women with PCOM was suggested by the glucose disappearance rate after insulin administration, although fasting insulin levels were not different (21). In PCOS, insulin resistance is detected more frequently with the use of postchallenge analysis than with HOMA (59). If this is also true in PCOM, the differences in insulin dynamics between women with PCOM and those with normal ovaries may well have been underestimated in the current study. The relationship of fasting insulin and HOMA with hCG-stimulated 17OHP and androgen levels in the current study suggests that insulin resistance and increased androgen secretion are linked in the setting of PCOM. As suggested by the studies by Norman et al. (13), it is possible that in the presence of PCOM, more severe abnormalities in insulin signaling may predispose to the menstrual irregularity that is characteristic of PCOS.
Both insulin and androgens decrease SHBG, and recent studies have shown that in a relatively lean population of PCOS patients, SHBG is a highly sensitive marker of changes in insulin sensitivity (60). In the current studies, SHBG levels were inversely related to both fasting insulin and HOMA, but not T, suggesting that in this population SHBG is primarily controlled by insulin. However, a functional polymorphism in the SHBG gene has been documented (61) that may conceivably contribute to differences in SHBG levels between ovulatory women with and without PCOM. This is of particular interest in light of evidence that prenatal exposure to increased androgens may predispose to PCOS (62). However, if this mechanism is responsible for PCOM, the current studies suggest that other mechanisms would also be required for the development of the anovulatory hyperandrogenism and gonadotropin abnormalities that are characteristic of PCOS.
In conclusion, PCOM in nonhirsute women with a history of confirmed ovulatory cycles is associated with normal E2, P4, and gonadotropin dynamics, but higher androgen and insulin levels and lower SHBG levels. Thus, although abnormal gonadotropin dynamics are not required for the development of PCOM or androgen hypersecretion, adrenal androgens, insulin resistance, or changes in SHBG may be involved in the development of this morphology. These findings suggest that PCOM represents the mildest form of ovarian hyperandrogenism. Longitudinal studies will be required to determine whether PCOM confers a propensity to the development of PCOS and, if so, what additional factors are required.
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Footnotes |
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Abbreviations: 4A, Androstenedione; DHEAS, dehydroepiandrosterone sulfate; E2, estradiol; EFP, early follicular phase; FT, free testosterone; hCG, human chorionic gonadotropin; HOMA, homeostasis model assessment; 17OHP, 17-hydroxyprogesterone; P4, progesterone; PCOM, polycystic ovarian morphology; PCOS, polycystic ovarian syndrome; T, testosterone.
Received September 12, 2003.
Accepted May 27, 2004.
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References |
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-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies. J Clin Endocrinol Metab 84:1028–1036 activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 335:617–623 activity and serum androgens. J Clin Endocrinol Metab 82:4075–4079This article has been cited by other articles:
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M. Mortensen, R. L. Rosenfield, and E. Littlejohn Functional Significance of Polycystic-Size Ovaries in Healthy Adolescents J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3786 - 3790. [Abstract] [Full Text] [PDF]
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S. Johnsen, S. E. Dolan, K. V. Fitch, K. M. Killilea, J. L. Shifren, and S. K. Grinspoon Absence of Polycystic Ovary Syndrome Features in Human Immunodeficiency Virus-Infected Women Despite Significant Hyperinsulinemia and Truncal Adiposity J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5596 - 5604. [Abstract] [Full Text] [PDF]
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S. A.R. Doi, M. Al-Zaid, P. A. Towers, C. J. Scott, and K. A.S. Al-Shoumer Irregular cycles and steroid hormones in polycystic ovary syndrome Hum. Reprod., September 1, 2005; 20(9): 2402 - 2408. [Abstract] [Full Text] [PDF]
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D.H. Abbott, D.K. Barnett, C.M. Bruns, and D.A. Dumesic Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum. Reprod. Update, July 1, 2005; 11(4): 357 - 374. [Abstract] [Full Text] [PDF]
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) and PCOM (n = 26; •).
) and those with PCOM (n = 19; 
) in the EFP, at midcycle (MCS), and in the midluteal phase (MLP). The P value refers to the overall difference between women with PCOM and those with normal ovaries using ANOVA, whereas the asterisks refer to the results of post hoc analysis in each cycle phase (*, P < 0.05). To convert T and free T to nanomoles per liter, multiply by 0.0346. To convert DHEAS to micromoles per liter, multiply by 0.02714.