Polycystic Ovary Syndrome (PCOS): State of the Art

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 15953

Special Issue Editor

Prof. Dr. Enrico Carmina
E-Mail Website
Guest Editor
Professor of Endocrinology, School of Medicine, University of Palermo, Palermo, Italy
Interests: PCOS; hyperandrogenism; non classic congenital adrenal hyperplasia; fertility; infertility; anovulation; hirsutism; alopecia; female pattern hair loss; acne; menstrual irregularities
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Special Issue Information

Dear Colleagues,

Polycystic ovary syndrome is a common disorder that encompasses very different clinical patterns and may be associated with increased risk for diabetes and cardiovascular diseases.

This Special Issue will focus on some important clinical problems, including the role of obesity and metabolic disorders in pathogenesis and in clinical evolution of the disorder. New possible classification of the syndrome based on genetic and clinical clusters will be discussed. The treatment of special clinical problems in PCOS will be reviewed and new data will be presented.

We invite contributions to this important project and encourage discussion on pathogenesis and the new possible classification of the polycystic ovary syndrome.

Prof. Dr. Enrico Carmina
Guest Editor

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Keywords

  • polycystic ovary syndrome
  • hirsutism
  • obesity
  • insulin resistance
  • amenorrhea
  • adult acne
  • female pattern hair loss
  • polycystic ovaries
  • anti-Mullerian hormone

Published Papers (10 papers)

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Research

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11 pages, 846 KiB  
Article
The LH:FSH Ratio in Functional Hypothalamic Amenorrhea: An Observational Study
J. Clin. Med. 2024, 13(5), 1201; https://doi.org/10.3390/jcm13051201 - 20 Feb 2024
Viewed by 317
Abstract
Background: In functional hypothalamic amenorrhea (FHA), luteinizing hormone and follicle-stimulating hormone levels show high interindividual variability, which significantly limits their diagnostic value in differentiating FHA from polycystic ovary syndrome (PCOS). Our aim was to profile the LH:FSH ratio in a large sample of [...] Read more.
Background: In functional hypothalamic amenorrhea (FHA), luteinizing hormone and follicle-stimulating hormone levels show high interindividual variability, which significantly limits their diagnostic value in differentiating FHA from polycystic ovary syndrome (PCOS). Our aim was to profile the LH:FSH ratio in a large sample of patients with well-defined FHA. Methods: This observational study included all consecutive patients with FHA presenting to the Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, between January 2017 and August 2023. The main parameters of interest were the LH level, the FSH level, and the LH:FSH ratio. In a subgroup analysis, we compared the LH:FSH ratio of patients with PCO morphology (PCOM) on ultrasound with that of patients without PCOM. Results: A total of 135 patients were included. Only a minority of patients revealed FSH and LH levels ≤ 2.0 mIU/mL (13% and 39%, respectively). Most patients (81.5%) had an LH:FSH ratio ≤ 1.0, while a minority (2.2%) had a ratio ≥ 2.1. The LH:FSH ratio was similar in patients with and without PCOM. Conclusion: In a well-defined FHA sample, the LH:FSH ratio was ≤ 1 in most patients. The LH:FSH ratio may prove useful in distinguishing FHA from PCOS but needs further investigation. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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13 pages, 1287 KiB  
Article
Reactive Hypoglycemia: A Trigger for Nutrient-Induced Endocrine and Metabolic Responses in Polycystic Ovary Syndrome
J. Clin. Med. 2023, 12(23), 7252; https://doi.org/10.3390/jcm12237252 - 23 Nov 2023
Viewed by 1440
Abstract
Polycystic ovary syndrome (PCOS) is an insulin-resistant state compensated for by the body via hyperinsulinemia. More than 50% of women with PCOS are obese and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Energy/caloric content as well as the nutrient [...] Read more.
Polycystic ovary syndrome (PCOS) is an insulin-resistant state compensated for by the body via hyperinsulinemia. More than 50% of women with PCOS are obese and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Energy/caloric content as well as the nutrient composition of one’s diet may also be important. This article will present a series of studies from our research comparing the effects of dietary protein vs. simple carbohydrates (CHOs). The results of the acute challenge studies demonstrate that simple CHO intake causes reactive hypoglycemia in one third of women with PCOS, especially among obese and insulin-resistant individuals. Symptoms of hypoglycemia are associated with secretion of cortisol and adrenal androgens. Simple CHOs suppress the hunger signal ghrelin for a shorter period. During weight loss, women who receive protein supplementation achieve more significant weight and fat mass losses. The amino acid compositions of the protein supplements do not affect the improvements in weight and insulin resistance. It is plausible that simple CHO intake leads to weight gain, or interferes with weight loss, by causing reactive hypoglycemia, triggering adrenal steroid secretion and thus leading to snacking. Since obese women with PCOS are more susceptible to reactive hypoglycemia, a vicious cycle is established. Restriction of simple CHOs may break this cycle. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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16 pages, 1231 KiB  
Article
An Evolutionary Model for the Ancient Origins of Polycystic Ovary Syndrome
J. Clin. Med. 2023, 12(19), 6120; https://doi.org/10.3390/jcm12196120 - 22 Sep 2023
Viewed by 1200
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in [...] Read more.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter–gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today’s contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today’s obesogenic environment. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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7 pages, 219 KiB  
Article
Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs
J. Clin. Med. 2023, 12(18), 5921; https://doi.org/10.3390/jcm12185921 - 12 Sep 2023
Cited by 2 | Viewed by 2778
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
14 pages, 1231 KiB  
Article
How to Choose the Optimal Starting Dose of Clomiphene Citrate (50 or 100 mg per Day) for a First Cycle of Ovulation Induction in Anovulatory PCOS Women?
J. Clin. Med. 2023, 12(15), 4943; https://doi.org/10.3390/jcm12154943 - 27 Jul 2023
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Abstract
Research question: Clomiphene citrate (CC) is one of the first-line treatments for ovulation induction in women with anovulatory polycystic ovary syndrome (PCOS). However, nearly 1 out of 2 women is resistant to 50 mg/day of CC. The objective of this study is to [...] Read more.
Research question: Clomiphene citrate (CC) is one of the first-line treatments for ovulation induction in women with anovulatory polycystic ovary syndrome (PCOS). However, nearly 1 out of 2 women is resistant to 50 mg/day of CC. The objective of this study is to investigate the clinical, biological, and/or ultrasound factors that may predict the resistance to 50 mg/day of CC in the first cycle of treatment in women with anovulatory PCOS. This would make it possible to identify PCOS patients to whom the dose of 100 mg/day would be offered as of the first cycle. Design: A retrospective and monocentric study was conducted on 283 women with anovulatory PCOS who required the use of ovulation induction with CC (903 cycles). Results: During the first cycle of treatment, 104 patients (36.8%) were resistant to 50 mg/day of CC. Univariate regression analysis showed that patients who resisted 50 mg/day of CC had significantly higher BMI, waist circumference, serum levels of AMH, total testosterone, Δ4-androstenedione, 17-OHP, and insulin (p < 0.05), compared to patients ovulating with this dose. Serum levels of SHBG were significantly lower in patients resistant to 50 mg/day (p < 0.05). After multivariate analysis, only AMH and SHBG remained statistically significant (p = 0.01 and p = 0.001, respectively). However, areas under the ROC curves were weak (0.59 and 0.68, respectively). Conclusion: AMH and SHBG are the only two parameters significantly associated with the risk of resistance to 50 mg/day of CC. However, no satisfactory thresholds have been established to predict resistance to 50 mg CC. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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9 pages, 252 KiB  
Article
Translation of the Modified Polycystic Ovary Syndrome Questionnaire (mPCOSQ) and the Polycystic Ovary Syndrome Quality of Life Tool (PCOSQOL) in Dutch and Flemish Women with PCOS
J. Clin. Med. 2023, 12(12), 3927; https://doi.org/10.3390/jcm12123927 - 08 Jun 2023
Viewed by 1796
Abstract
This study aims to determine the test–retest reliability and to confirm the domain structures of the Dutch version of the modified polycystic ovary syndrome questionnaire (mPCOSQ) and the Polycystic Ovary Syndrome Quality of Life Scale (PCOSQOL) in Dutch and Flemish women with Polycystic [...] Read more.
This study aims to determine the test–retest reliability and to confirm the domain structures of the Dutch version of the modified polycystic ovary syndrome questionnaire (mPCOSQ) and the Polycystic Ovary Syndrome Quality of Life Scale (PCOSQOL) in Dutch and Flemish women with Polycystic Ovary Syndrome (PCOS). PCOS patients were contacted with a request to complete both questionnaires (including additional demographic questions) online in their home environment on T0 and on T1. The study was approved by the Ethics Committee of Erasmus Medical Centre and of Ghent University Hospital. In this study, 245 participants were included between January and December 2021. The mPCOSQ has excellent internal consistency (α: 0.95) and a high to excellent Intraclass Correlation Coefficient (ICC) for all six domains (ICC: 0.88–0.96). The PCOSQOL demonstrates excellent internal consistency (α: 0.96) and ICC (ICC: 0.91–0.96) for all four domains. The original six-factor structure of the mPCOSQ is partly confirmed. An extra domain is added to the PCOSQOL which included coping items. Most women have no preference for one of the two questionnaires (55.9%). In conclusion, The Dutch mPCOSQ and PCOSQOL are reliable and disease-specific QoL measures for women with PCOS. Both questionnaires are recommended for clinical practice. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
13 pages, 1322 KiB  
Article
Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial
J. Clin. Med. 2023, 12(8), 2827; https://doi.org/10.3390/jcm12082827 - 12 Apr 2023
Viewed by 1724
Abstract
This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined [...] Read more.
This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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15 pages, 1236 KiB  
Article
The Effect of Tailored Short Message Service (SMS) on Physical Activity: Results from a Three-Component Randomized Controlled Lifestyle Intervention in Women with PCOS
J. Clin. Med. 2023, 12(7), 2466; https://doi.org/10.3390/jcm12072466 - 23 Mar 2023
Viewed by 1382
Abstract
This analysis of secondary outcome measures of a randomized controlled trial was conducted to study the effect of a one-year three-component (cognitive behavioural therapy, diet, exercise) lifestyle intervention (LSI), with or without additional Short Message Service (SMS) support, on physical activity and aerobic [...] Read more.
This analysis of secondary outcome measures of a randomized controlled trial was conducted to study the effect of a one-year three-component (cognitive behavioural therapy, diet, exercise) lifestyle intervention (LSI), with or without additional Short Message Service (SMS) support, on physical activity and aerobic capacity in overweight or obese women with polycystic ovary syndrome (PCOS). Women diagnosed with PCOS and a BMI > 25 kg/m2 were randomly assigned to LSI with SMS support (SMS+, n = 60), LSI without SMS support (SMS−, n = 63) or care as usual (CAU, n = 60) in order to lose weight. Based on results from the International Physical Activity Questionnaire (IPAQ), we found a significant within-group increase after one year for SMS+ in the high physical activity category (+31%, p < 0.01) and sitting behaviour decreased (Δ −871 min/week, p < 0.01). Moreover, the peak cycle ergometer workload increased within SMS+ (Δ +10 watts, p < 0.01). The SMS+ group also demonstrated a significantly different increase in walking metabolic equivalent of task minutes (METmin)/week compared with CAU after one year (Δ 1106 METmin/week, p < 0.05). Apart from this increase in walking activity, no other between-group differences were found in this trial. Overall, based on within-group results, SMS support seemed to help with improving physical activity and aerobic capacity and decreasing sedentary behaviour. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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15 pages, 1071 KiB  
Article
Pregnancy Outcomes in Women with PCOS: Follow-Up Study of a Randomized Controlled Three-Component Lifestyle Intervention
J. Clin. Med. 2023, 12(2), 426; https://doi.org/10.3390/jcm12020426 - 05 Jan 2023
Cited by 1 | Viewed by 2940
Abstract
Women with polycystic ovary syndrome (PCOS) and excess weight often present with reproductive derangements. The first-line treatment for this population is a multi-component lifestyle intervention. This follow-up study of a randomized controlled trial based on data from the Dutch Perinatal registry was conducted [...] Read more.
Women with polycystic ovary syndrome (PCOS) and excess weight often present with reproductive derangements. The first-line treatment for this population is a multi-component lifestyle intervention. This follow-up study of a randomized controlled trial based on data from the Dutch Perinatal registry was conducted to study the effect of a one-year three-component (cognitive behavioral therapy, healthy diet, and exercise) lifestyle intervention on pregnancy outcomes in women with PCOS and overweight or obesity. Women diagnosed with PCOS, a BMI ≥ 25 kg/m², and a wish to conceive were randomized to either three-component lifestyle intervention (LSI, n = 123), and care as usual (CAU, n = 60) where they were encouraged to lose weight autonomously. Conception resulting in live birth was 39.8% (49/123) within LSI and 38.3% (23/60) within CAU (p = 0.845). In total, 58.3% conceived spontaneously. Gestational diabetes (LSI: 8.2% vs. CAU: 21.7%, p = 0.133), hypertensive disorders (LSI: 8.2% vs. CAU 13.0%, p = 0.673), and preterm birth (LSI: 12.2% vs. CAU: 17.4%, p = 0.716) rates were all lower in LSI compared to CAU. This follow-up study showed no significant differences in conception resulting in live birth rates between LSI and CAU. Nonetheless, a large proportion eventually conceived spontaneously. Moreover, after LSI, the number of uneventful pregnancies was lower compared to care as usual. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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Review

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12 pages, 249 KiB  
Review
The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review
J. Clin. Med. 2024, 13(4), 1056; https://doi.org/10.3390/jcm13041056 - 13 Feb 2024
Viewed by 380
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including insufficient treatment options. Over the past 88 years, multiple hormonal and non-hormonal medications have been tried to treat the various components of this syndrome and there is no FDA (Food and Drug Administration)-approved medication specifically for PCOS yet. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have a unique mechanism of inhibiting the coupled reabsorption of sodium and glucose in renal proximal convoluted tubules. This review aims to examine the efficacy and side-effect profile of SGLT-2 inhibitors in patients with PCOS. In a limited number of studies, SGLT-2 inhibitors appear to be effective in improving menstrual frequency, reducing body weight and total fat mass, lowering total testosterone and DHEAS levels, and improving some glycemic indices in women with PCOS. SGLT2 inhibitors are generally well tolerated. With future research, it is possible that SGLT-2 inhibitors could become a key therapeutic option for PCOS. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art)
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