Polycystic ovary syndrome (PCOS) affects 6–10% of women in reproductive age and is characterized by hyperandrogenism, insulin resistance, and chronic anovulation [1]. It is a heterogeneous syndrome with not completely understood etiology that is related to a complex interaction between metabolic, endocrine, genetic, and environmental factors. Increasing evidence suggests that insulin resistance and secondary hyperinsulinemia play a key synergistic role with hyperandrogenism in the development and maintenance of metabolic alterations and anovulation or irregular cycles in both obese and lean patients with PCOS [2]. On that basis, current treatment strategies aim at reducing insulin resistance in patients with PCOS and, consequently, to reach a reduction of compensatory hyperinsulinemia, improving metabolic and ovulatory features [3–5]. Insulin-sensitizer drugs are the recommended first-line therapy according to recent guidelines [6] for women with PCOS and metabolic abnormalities [7–9] with the aim at improving fertility [10–13], although physical activity and lifestyle change should be considered the first steps in overweight and obese PCOS patients to achieve weight loss [14, 15].
In this scenario, we are honored to introduce this special issue, which contains five articles that may shed new light on the topic. In particular, three articles are focused on metabolic disturbances in PCOS women: the first one (“Free Testosterone Reflects Metabolic as well as Ovarian Disturbances in Subfertile Oligomenorrheic Women”) found that sex hormone-binding globulin and calculated free testosterone are associated with both ovarian ultrasound and metabolic parameters, such as the body mass index (BMI) and insulin resistance, suggesting a pivotal role for androgen excess in PCOS-related subfertility and ovulatory dysfunction; the second article (“Pericardial Fat Relates to Disturbances of Glucose Metabolism in Women with the Polycystic Ovary Syndrome, but Not in Healthy Control Subjects”) found that pericardial fat measured using 1H-magnetic resonance spectroscopy and imaging is positively related to atherogenic lipid profiles, BMI, waist circumference, and liver fat in women with PCOS, suggesting it as a potential noninvasive tool to predict metabolic prognosis in this population; the third article (“Low-Dose Spironolactone-Pioglitazone-Metformin Normalizes Circulating Fetuin-A Concentrations in Adolescent Girls with Polycystic Ovary Syndrome”) highlights that a low-dose combination of insulin sensitizers and an antiandrogen is able to normalize fetuin-A levels in adolescent girls with PCOS. Considering that high levels of fetuin-A have been associated with greater risks for type 2 diabetes and with features of metabolic syndrome, this treatment may significantly reduce metabolic consequences and prevent acute events.
Besides these three articles related to metabolic disturbances and their treatment, another paper (“The Place of In Vitro Maturation in PCO/PCOS”) depicted a clear and accurate summary of available evidence regarding the optimization of culture media, laboratory protocols, pregnancy rates, and neonatal outcomes following in vitro maturation (IVM) of human oocytes in PCOS women, which are known to have a variable incidence of infertility and worse outcomes following assisted reproductive technology.
Finally, the last paper (“Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy Controls”) investigated differences in the uterine artery pulsatility index (UtAPI) between pregnant women with PCOS and healthy controls and explored the possible effects of metformin on this parameter. Interestingly, the authors found that there was no difference in the UtAPI between women with PCOS and healthy controls in the first and second trimesters of pregnancy; in addition, metformin was not found to have an immediate effect on the UtAPI.
Overall, the manuscripts published in this special issue add significant and novel elements for the understanding of the etiology, pathophysiology, diagnosis, and treatment of this complex and multifaceted syndrome. We offer these new insights to the readers, hoping that they will stimulate further debate and address new fields of investigation in the next future.
Disclosure
The authors alone are responsible for the content and writing of the paper.
Conflicts of Interest
The authors have no proprietary, financial, professional, or other personal interests of any nature in any product, service, or company.
Antonio Simone Laganà
Salvatore Giovanni Vitale
Marco Noventa
Amerigo Vitagliano
References
- 1.Lizneva D., Suturina L., Walker W., Brakta S., Gavrilova-Jordan L., Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertility and Sterility. 2016;106(1):6–15. doi: 10.1016/j.fertnstert.2016.05.003. [DOI] [PubMed] [Google Scholar]
- 2.Rosenfield R. L., Ehrmann D. A. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocrine Reviews. 2016;37(5):467–520. doi: 10.1210/er.2015-1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Paul C., Laganà A. S., Maniglio P., Triolo O., Brady D. M. Inositol’s and other nutraceuticals' synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives. Gynecological Endocrinology. 2016;32(6):431–438. doi: 10.3109/09513590.2016.1144741. [DOI] [PubMed] [Google Scholar]
- 4.Muscogiuri G., Palomba S., Laganà A. S., Orio F. Current insights into inositol isoforms, Mediterranean and ketogenic diets for polycystic ovary syndrome: from bench to bedside. Current Pharmaceutical Design. 2016;22(36):5554–5557. doi: 10.2174/1381612822666160720160634. [DOI] [PubMed] [Google Scholar]
- 5.Laganà A. S., Rossetti P., Buscema M., et al. Metabolism and ovarian function in PCOS women: a therapeutic approach with inositols. International Journal of Endocrinology. 2016;2016:9. doi: 10.1155/2016/6306410.6306410 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility. 2004;81(1):19–25. doi: 10.1016/j.fertnstert.2003.10.004. [DOI] [PubMed] [Google Scholar]
- 7.Pizzo A., Laganà A. S., Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecological Endocrinology. 2013;30(3):205–208. doi: 10.3109/09513590.2013.860120. [DOI] [PubMed] [Google Scholar]
- 8.Laganà A. S., Rossetti P., Sapia F., et al. Evidence-based and patient-oriented inositol treatment in polycystic ovary syndrome: changing the perspective of the disease. International Journal of Endocrinology and Metabolism. 2017;15(1, article e43695) doi: 10.5812/ijem.43695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Laganà A. S., Barbaro L., Pizzo A. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-chiro-inositol. Archives of Gynecology and Obstetrics. 2015;291(5):1181–1186. doi: 10.1007/s00404-014-3552-6. [DOI] [PubMed] [Google Scholar]
- 10.Vitale S. G., Rossetti P., Corrado F., et al. How to achieve high-quality oocytes? The key role of Myo-inositol and melatonin. International Journal of Endocrinology. 2016;2016:9. doi: 10.1155/2016/4987436.4987436 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Laganà A. S., Vitagliano A., Noventa M., Ambrosini G., D’Anna R. Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Archives of Gynecology and Obstetrics. 2018;298(4):675–684. doi: 10.1007/s00404-018-4861-y. [DOI] [PubMed] [Google Scholar]
- 12.Gulino F. A., Leonardi E., Marilli I., et al. Effect of treatment with myo-inositol on semen parameters of patients undergoing an IVF cycle: in vivo study. Gynecological Endocrinology. 2015;32(1):65–68. doi: 10.3109/09513590.2015.1080680. [DOI] [PubMed] [Google Scholar]
- 13.Laganà A. S., Garzon S., Casarin J., Franchi M., Ghezzi F. Inositol in polycystic ovary syndrome: restoring fertility through a pathophysiology-based approach. Trends in Endocrinology and Metabolism. 2018;29(11):768–780. doi: 10.1016/j.tem.2018.09.001. [DOI] [PubMed] [Google Scholar]
- 14.Dokras A., Sarwer D. B., Allison K. C., et al. Weight loss and lowering androgens predict improvements in health-related quality of life in women with PCOS. The Journal of Clinical Endocrinology and Metabolism. 2016;101(8):2966–2974. doi: 10.1210/jc.2016-1896. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Legro R. S., Dodson W. C., Kunselman A. R., et al. Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. The Journal of Clinical Endocrinology and Metabolism. 2016;101(7):2658–2666. doi: 10.1210/jc.2016-1659. [DOI] [PMC free article] [PubMed] [Google Scholar]