Four experts discussed advances in the diagnosis and treatment of women with polycystic ovary syndrome (PCOS) during a Scientific Sessions symposium on Saturday, June 26.
The session, Polycystic Ovary Syndrome (PCOS)—Towards Personalized Medicine—Advances in PCOS Diagnosis and Care, can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.
“PCOS is a significant women’s health concern,” said Jerome F. Strauss III, MD, PhD, Professor of Obstetrics and Gynecology, Virginia Commonwealth University. “Reproductive endocrine phenotypes form the basis of most commonly used diagnostic criteria. The genetic component is relatively new, but we can now manipulate and change the biochemical phenotype of both normal and PCOS theca cells.”
Familial studies into clustering and heritability revealed the genetic underpinnings of PCOS in the 1990s, and researchers have now identified more than 20 loci associated with the syndrome. The DENND1A gene is at the nexus of ligands critical to ovarian function and gene regulators of biosynthesis, Dr. Strauss said. The gene codes for two primary proteins, version 1 and version 2.
“Version 2 expression is enhanced in theca cells from women with PCOS,” he explained. “If you force-enhanced version 2 expression in normal theca cells, you get greatly enhanced production of testosterone and other androgens seen in PCOS in both cell culture and in mouse models. There may be an immunotherapy approach to PCOS by neutralizing expression of the version 2 protein.”
Erik A. Richter, MD, DMSci, Professor and Section Head of Molecular Physiology at the University of Copenhagen, Denmark, discussed the effects of exercise on PCOS patients. Exercise training improves physical fitness and psychological well-being in lean women who have PCOS, he said, but exercise does not improve the metabolic complications that put women with PCOS at an elevated risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease.
A 14-week course of aerobic and weight training designed to improve fitness without weight loss in lean women with and without PCOS showed many of the expected physical benefits, Dr. Richter explained. Both groups had similar reductions in total body fat, increases in lean body mass, and improvements in oxygen uptake. But women with PCOS showed few significant metabolic changes, he said.
Total testosterone and free testosterone both decreased with exercise but did not normalize in the PCOS group. Glucose tolerance improved in the control group and remained unchanged in the PCOS group. Likewise, the control group showed improvement in insulin response, insulin sensitivity, insulin signaling, and muscle glucose intake while the PCOS group did not.
“The physical changes were much appreciated by the majority of women in both groups,” Dr. Richter reported. “The women with PCOS were very happy with the effects of exercise training on their bodies [and] reported feeling more comfortable in their bodies, more feminine, with more regular menstruation.”
Looking beyond exercise, there are currently no approved medications for PCOS. However, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists are commonly used off-label to treat the triad of amenorrhea, obesity, and hirsutism, noted Karen Elkind-Hirsch, MS, PhD, Scientific Director of Research, Woman’s Hospital Research Center and Endocrine Clinic.
A handful of studies of DPP-4 inhibitors have shown impressive results in glucose tolerance, menstrual cycle frequency and regularity, and weight gain or regain, but little change in androgen profiles, Dr. Elkind-Hirsch added. Trials with GLP-1 receptor agonists show more profound metabolic improvements as well as improvements in androgen and lipid profiles, she said.
“Probably due to the greater efficacy in weight loss, patient satisfaction is greater with GLP-1 receptor agonists than with DPP-4 inhibitors,” Dr. Elkind-Hirsh said. “But we don’t know anything about potential intervention before conception to improve fertility rates. We need more and larger trials.”
Anuja Dokras, MD, PhD, Professor of Obstetrics and Gynecology at the Center for Reproduction and Women’s Health, University of Pennsylvania Perelman School of Medicine, discussed mood changes when treating metabolic health in PCOS. The metabolic complications of PCOS are well known, she said, but mental health complications are less recognized.
“There are multiple reproductive and metabolic comorbidities associated with PCOS, as well as anxiety, depression, negative body image, low self-esteem, psychosexual dysfunction, eating disorders, and poor quality of life,” she said. “Many of these comorbidities are exaggerated with obesity, a common complication with PCOS.”
Just as women with PCOS have increased risk for impaired glucose tolerance, type 2 diabetes, gestational diabetes, metabolic syndrome, and cardiovascular disease, they are at increased risk for multiple psychiatric disorders, Dr. Dokras continued. Lifestyle modification and hormonal contraception to improve menstrual regularity can also improve reproductive, metabolic, and psychiatric outcomes, she said.
“There are robust data for the high prevalence of anxiety and depression in PCOS. Obesity and body image are useful targets for intervention,” Dr. Dokras said. “Just as we screen for metabolic symptoms, we need to screen these women for depressive and anxiety symptoms and make the necessary interventions. There is a very close connection between metabolic health and mental health.”