Carmina, E., & Lobo, R. A. (1999). Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertility and Sterility, 71(2), 319-322. https://doi.org/10.1016/s0015-0282(98)00455-5
Carmina E, Lobo RA. Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertil Steril. 1999;71(2):319-322. doi:10.1016/s0015-0282(98)00455-5
Carmina, E., and R. A. Lobo. "Do hyperandrogenic women with normal menses have polycystic ovary syndrome?" Fertility and Sterility, vol. 71, no. 2, 1999, pp. 319-322.
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Hyperandrogenic women with normal periods may still have PCOS
In 58 women with high androgen levels and self-reported normal periods, 43 could be considered to have PCOS. This was a prospective observational study at one academic practice. Twelve of the women were not ovulating on progesterone testing. Of the 46 who were, 31 had PCOS-like ovaries or hormone responses. PCOS is also called PMOS (polyendocrine metabolic ovarian syndrome).
Key Findings
Twelve of 58 women (20.7%) did not ovulate across two consecutive cycles, even though they reported normal menses.
Polycystic ovaries on ultrasound appeared in 11 of the 12 women who were not ovulating (91%) and in 19 of the 46 who were ovulating (42%).
An exaggerated 17-hydroxyprogesterone response to a leuprolide acetate test appeared in 10 of 12 women not ovulating (83%) and 24 of 46 ovulating (52%).
Of the 46 ovulating women, 31 (67%) had polycystic ovaries, an exaggerated hormone response, or both. Fifteen (33%) had neither.
Counting both groups, 43 of 58 women (74%) could be considered to have PCOS.
Interpretation
The authors studied 58 consecutive new patients at one academic practice in 1996 and 1997. All had high androgen levels and reported normal menses. Progesterone tests, repeated in the next cycle when low, checked ovulation. The authors say 74% of these women could be considered to have PCOS. They reach that number with a liberal reading that accepts ovulation alongside polycystic ovaries or an exaggerated hormone response. They still name high androgens plus chronic lack of ovulation as the usual criteria. The authors say the cause of excess androgens in ovulating women without PCOS features cannot be established at this time.
RRM Context
Regular bleeding can occur without ovulation. Twelve of these 58 women had normal menses and no ovulation on progesterone testing. Restorative reproductive medicine asks whether ovulation happened and what drives the excess androgens. The authors say that cause cannot be established at this time for one third of the ovulating women.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To determine the prevalence of polycystic ovary syndrome (PCOS) among hyperandrogenic women who report normal menses.
Design
Prospective observational study.
Setting
Academic practice in reproductive endocrinology.
Patients
Fifty-eight consecutively seen new patients with hyperandrogenism who reported normal menses.
Interventions
Ovulatory status was assessed with timed serum progesterone measurements. The following tests also were carried out: vaginal ultrasound examination; measurement of the ovarian response of 17-hydroxyprogesterone (17-OHP) after the administration of leuprolide acetate, 1 mg SC; and determination of fasting serum LH, FSH, E2, 17-OHP, insulin, and androgen levels.
Main Outcome Measures
Determination of ovulatory status, polycystic appearance of ovaries, and increased response of 17-OHP to leuprolide acetate.
Results
Twelve (20.7%) of the hyperandrogenic women were anovulatory and met the usual criteria for the diagnosis of PCOS. The ovulatory patients had lower serum total and unbound testosterone levels. Thirty-one (53.4%) of the ovulatory women had polycystic ovaries on ultrasound examination and/or an increased 17-OHP response to leuprolide acetate, suggesting the diagnosis of PCOS despite the presence of ovulation. Considering both the anovulatory and ovulatory patients, 74% of the hyperandrogenic women studied could have PCOS.
Conclusions
The data suggest that most (74%) hyperandrogenic women who report normal menses have evidence for the diagnosis of PCOS.
Carmina E et al., 2026·Journal of clinical medicine·Free full text on PubMed Central
Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.
Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
Carmina E et al., 2023·Journal of clinical medicine·Free full text on PubMed Central
In spite of the widespread use of lifestyle modifications programs, many patients with PCOS are obese and prevalence of obesity in PCOS remains high. In this study, we present the data on the use of semaglutide, an incretin mimetic drug, in obese PCOS patients who were unresponsive to a lifestyle modification program. Twenty-seven obese patients with a diagnosis of PCOS, who did not reduce their body weight by a lifestyle modification program, were included in this study and treated by semaglutide, 0.5 mg subcutaneously once a week. After three months of treatment, an improvement in body weight with a mean decrease in body weight of 7.6 kg and a mean BMI loss of 3.1 was observed, while very few side effects were reported. Almost 80% of the studied obese PCOS patients obtained at least a 5% decrease in their body weight. Only a few patients (22%) obtained a decrease in body weight lower than 5% and were considered non-responsive to semaglutide, at least at the used doses. These patients presented a more severe obesity than responsive patients. Independently of results on body weight, and in patients who did not obtain a 5% decrease in their body weight, insulin basal values decreased, and HOMA-IR improved. Fasting blood glucose normalized in 80% of semaglutide-treated IFG PCOS women. In patients who were responsive to semaglutide (weight loss > 5%), the treatment was continued for additional three months. Weight loss slowed but continued and, at the end of the six months of therapy, the mean body weight loss was 11.5 kg and mean BMI reduced from 34.4 to 29.4. A total of 80% of responsive patients normalized menstrual cycles. In conclusion, treatment with semaglutide, at low doses, significantly reduces body weight in almost 80% of obese PCOS patients who were unresponsive to a previous lifestyle plan. It is often associated with the normalization of menstrual cycles, and these important results are obtained with very few side effects.
Outcomes and Effectiveness · Cumulative Versus Per Cycle Reporting
Luke B et al., 2012·The New England journal of medicine·Free full text on PubMed Central
Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).
To determine pharmacokinetic and endometrial effects of vaginally delivered micronized P. Functionally agonadal estrogen-replacement recipients received either micronized P administered vaginally or bi-daily IM injections of P. Hourly blood samples were obtained, from baseline to 6 hours after the initial dose of P and again on simulated cycle day 21 when transvaginal ultrasound (US) measurements and tissue samples of the endometrium were performed. Blood and tissue samples were assayed for P. Endometrial histology, estrogen receptor (ER) and P receptor (PR) contents were evaluated. University of Southern California School of Medicine, Los Angeles, California. Twenty functionally agonadal and four normally ovulating women. Delivery differences were assessed by [1] endometrial P concentrations; [2] USs; [3] histologic datings; [4] ER and PR contents, and [5] serum P levels. Endometrial P concentrations were higher with vaginally administered P than endometrial concentrations observed in normal ovulatory women or women who consistently had the highest serum P after IM administration (11.50 +/- 2.60 versus 1.40 +/- 0.40 versus 0.30 +/- 0.10 ng/mg protein [36.56 +/- 8.27 versus 4.45 +/- 1.27 versus 0.95 +/- 0.32 nmol/L], respectively). After 7 days of P, no differences between either treatment regimen and control groups were detected by histologic, ultrasonographic, or immunocytochemical receptor analyses. Vaginal micronized P enhances P delivery to the uterus compared with a standard IM regimen and results in a synchronous secretory endometrial histology in agonadal women preparing for embryo donation.
Adams J et al., 1986·Br Med J (Clin Res Ed)·Free full text on PubMed Central
Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate.
To investigate the relationship between the ovarian stromal area and clinical hormonal characteristics in women with polycystic ovary syndrome (PCOS). Twenty-eight women with PCOS (group 1) and 26 healthy women (group 2) participated in this study. For measuring the ovarian stromal area, transvaginal ultrasonography was performed on all women during the early follicular phase of the menstrual cycle. Venous blood was sampled from the women to determine serum follicle stimulating hormone, luteinizing hormone (LH), estradiol, androstenedione, free testosterone (FT), total testosterone (TT), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate, and fasting insulin and glucose levels. Two-tailed t and Pearson correlation tests were used for statistical analysis. Women with PCOS were heavier, and their serum FT, TT and LH levels were significantly higher than in the normals (P < .001, P < .012 and P < .001, respectively). The ovarian stromal area measured by transvaginal ultrasonography was also significantly larger than in the normals (P < .001). Only basal serum insulin levels seemed to correlate positively with the ovarian stromal area in women with PCOS (r = .43 P = .09). Although transvaginal ultrasonography has played an important role in the evaluation of women with PCOS, we could not demonstrate a relationship between the ovarian stromal area and hormonal characteristics of PCOS. Therefore, transvaginal ultrasonography and hormonal parameters must be used as complementary diagnostic methods in women with PCOS.
To study the prevalence of polycystic ovaries (PCO) in women of reproductive age. A total of 189 healthy volunteers aged 20-45 years were examined. The subjects were divided into two groups according to age: < or =35 and > or =36 years. Transvaginal ultrasonography was performed and blood samples were collected on cycle day 1-6. The prevalence of PCO in the entire study population was 14.2% (27/189). In the age group of < or =35 years the prevalence was 21.6% (19/88) and in the age group of > or =36 years 7.8% (8/101). Compared to women with normal ovaries, those with PCO had significantly higher serum testosterone (T) concentrations. Women with PCO tended to have lower serum FSH concentrations and higher LH/FSH ratios than controls. Women with PCO had significantly more irregular cycles (44% vs. 19%, p=0.001) and problems in conceiving (25.9% vs. 9.2%, p=0.01) than women with normal ovaries. The findings demonstrate that the prevalence of PCO in healthy women varies with age, being more common among women aged < or =35 years than in those aged > or =36 years. Although the hormonal parameters and clinical findings among women with PCO mimicked those of PCOS, it remains unclear if these women will later develop full-blown syndrome.
Sjaarda LA et al., 2014·J Clin Endocrinol Metab·Free full text on PubMed Central
Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS) in women with irregular menses, yet the relationship between androgens and ovarian dysfunction remains poorly understood in eumenorrheic women. The objective of the study was to evaluate whether sporadic anovulation was associated with higher T and anti-müllerian hormone (AMH; marker of ovarian follicle count) concentrations in eumenorrheic women.
This was a prospective cohort study from 2005 to 2007.
The study was conducted at the University of Buffalo in western New York state. A total of 259 eumenorrheic women without a self-reported history of infertility, PCOS, or other endocrine disorder participated in the study. Total T and AMH were measured five to eight times per cycle for one (n = 9) or two (n = 250) cycles per woman (n = 509 cycles) with timing of menstrual cycle phase assisted by fertility monitors. Anovulatory cycles were defined biochemically by progesterone and LH concentrations. Repeated-measures ANOVA was conducted on log-transformed data with adjustment for age. Compared with ovulatory cycles (n = 467), sporadic anovulatory cycles (n = 42) had marginally higher total and significantly higher free T [mean 23.7 ng/dL (95% confidence interval [CI] 21.4-26.3) vs 21.6 ng/dL (95% CI 20.9-22.3), P = .08, and 0.36 ng/dL (95% CI 0.33-0.40) vs 0.32 ng/dL (95% CI 0.31-0.33), P = .02, respectively] during menses and also throughout the luteal phase (P < .01 for all). Women with higher T had elevated AMH concentrations, increased reporting of a history of acne requiring medical treatment, but not increased hirsutism. Mechanisms of androgen-related ovulatory dysfunction that characterize PCOS in women with menstrual disturbances may occur across a continuum of T concentrations, including in eumenorrheic women without clinical hyperandrogenism.
PMID 9988405 9988405 DOI 10.1016/s0015-0282(98)00455-5 10.1016/s0015-0282(98)00455-5 Carmina et al. 1999, Carmina 1999
Cite this article
Carmina, E., & Lobo, R. A. (1999). Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertility and Sterility, 71(2), 319-322. https://doi.org/10.1016/s0015-0282(98)00455-5
Carmina E, Lobo RA. Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertil Steril. 1999;71(2):319-322. doi:10.1016/s0015-0282(98)00455-5
Carmina, E., and R. A. Lobo. "Do hyperandrogenic women with normal menses have polycystic ovary syndrome?" Fertility and Sterility, vol. 71, no. 2, 1999, pp. 319-322.
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