PCOS DISCOVERIES: Men with Genetic Risk Factors & Black Women at Greater Odds for Cardiometabolic Diseases

Two new studies presented at the annual ENDO 2021 meeting (March 20-23), the Endocrine Society’s annual meeting, provides valuable insight into polycystic ovary syndrome (PCOS). The first study found that men with the genetic risk factors for PCOS can develop the same characteristics of the disease. This surprising study leads researchers to believe that, despite the name of the disease, the primary cause of PCOS may not be the ovaries.

The second study found that Black women with polycystic ovary syndrome (PCOS) have higher risk factors for heart disease, diabetes and stroke as compared to white women. The study calls for greater public awareness and diversity considerations when choosing participants for PCOS studies. The researchers noted that most studies included primarily white women.

PCOS is a common disorder characterized by irregular menstrual periods, disruption of normal metabolism and elevated testosterone levels. PCOS affects up to 10% of all women of reproductive age. The disorder can lead to obesity, diabetes and cardiovascular disease, which are often life-long conditions.

Men with Genetics Risk Factors for PCOS

The study reported that men who have genetic risk factors for PCOS face an increased risk of obesity, diabetes and cardiovascular disease as well as male pattern baldness.

In the abstract, researchers note the following:

“Both ovarian-related and ovarian-independent factors have been implicated in the pathogenesis of PCOS, but it remains to be determined which are the inciting events and which are the secondary consequences. Studies of male relatives of women with PCOS have proposed a male counterpart of PCOS, which suggests that PCOS is not always a primary disorder of female reproduction, but rather can be, at least in part, a condition of cardiometabolic dysregulation and hyperandrogenism, with ovarian dysfunction as a secondary consequence.”

Because men do not have ovaries, the findings show for the first time that the primary cause of PCOS may not be linked to the ovaries.

“The treatment of PCOS is limited by our incomplete understanding of the disorder,” said lead researcher Jia Zhu, M.D., of Boston Children’s Hospital. “Identifying the different causes for PCOS provides insights into the mechanisms of disease and is the first step in identifying future targets for treatment of the disorder.”

The researchers used genetic data from 176,360 men in the United Kingdom to estimate genetic susceptibility for PCOS. They tested for associations with metabolic disorders (obesity, diabetes, and cardiovascular disease) and male-pattern baldness. Men who had a high genetic risk score for PCOS had increased risk of obesity, diabetes, cardiovascular disease and male-pattern baldness.

  • Men who carried a high PCOS polygenic risk scores (PRS, top 20%) had a 17% increased risk of obesity defined as BMI ≥30 kg/m2 (OR 1.17, 95% confidence interval [CI] 1.14-1.20, p=1.3×10-30),
  • 15% increased risk of type 2 diabetesmellitus (OR 1.15, 95% CI 1.09-1.20, p=5.3×10-8),
  • 5% increased risk of coronary artery disease (OR 1.05, 95% CI 1.01-1.09, p=0.03), and
  • 5% increased risk for androgenic alopecia (OR 1.05, 95% CI 1.01-1.08, p=0.01).
  • BMI, hemoglobin A1c, triglycerides, and the free androgen index all increased across deciles of the PRS, while HDL and sex hormone binding globulin (SHBG) decreased across PRS deciles (p all <0.001).

“By demonstrating that genetic risk factors for PCOS are associated with obesity, diabetes and cardiovascular disease and male-pattern baldness in men, we show that these genetic risk factors do not require ovaries to result in the characteristics of PCOS,” Zhu said.

“Thus, at least in some cases, the reproductive dysfunction of PCOS may be caused by biological mechanisms common to both men and women. Future studies of the genetic risk factors for PCOS could help us to better understand the causes and potential treatment targets for PCOS,” he said.

Conclusion/ “By demonstrating associations between PCOS genetic risk factors and cardiometabolic dysfunction and androgenic conditions in men, we have shown that these genetic risk factors can act independently of ovarian function. Thus, at least in some cases, the reproductive dysfunction of PCOS in women may arise secondarily from disruption of biological pathways common to both men and women. Future dissection of these biological pathways will further inform efforts to identify pathological mechanisms underlying PCOS.”

Black Women with PCOS at Greater Risk for Cardiometabolic Diseases

PCOS, Black women

In order to find out whether Black women with PCOS share the same health risks as white women, Maryam Kazemi, Ph.D., a Postdoctoral Associate in Professor Marla Lujan’s laboratory in the Division of Nutritional Sciences at Cornell University in Ithaca, N.Y. conducted a systematic review of all available data on the risk of heart disease, diabetes and stroke. She looked at health disparities between Black and white women with PCOS in the United States. The review included 11 studies, with a total of 2,851 women (652 Black and 2,199 white).

The analysis found Black women with PCOS have a poorer cardiometabolic risk profile than white women, including higher insulin levels and more insulin resistance (risk factors for diabetes), and increased blood pressure, despite lower triglyceride levels than white women.

Dr Kazemi reported a disproportionate risk of complications in Black women with PCOS in the United States, which highlights the need to fully identify and address health disparities in women with PCOS.

Highlights:

  1. Black women with polycystic ovary syndrome have a greater tendency for an adverse cardiometabolic risk profile (increased insulin, homeostatic model assessment of insulin resistance, and systolic blood pressure) despite lower triglycerides than white women.
  2. The observations support the consideration of these disparities for diagnostic, monitoring, and management practices in black women and for future guideline recommendations.
  3. Given the heterogeneity among studies, future research should address the relative contributions of biologic, environmental, socioeconomic, and healthcare factors to the observed disparities.
  4. Furthermore, longitudinal research is required to address patient-pressing complications, including cardiovascular events and mortality rate in black women with polycystic ovary syndrome as a high-risk yet understudied population.

“Our findings support the need to increase public awareness about the disproportionate burden of cardiometabolic risk in young Black women with PCOS,” said Kazemi. “These findings have implications for improving the sensitivity of clinical assessments in Black women to avoid underestimating cardiovascular risk in women with PCOS.”

Conclusion/ “Black women with polycystic ovary syndrome have a greater tendency for an adverse cardiometabolic risk profile (increased insulin, homeostatic model assessment of insulin resistance, and systolic blood pressure) despite lower triglycerides than white women. Our observations support the consideration of these disparities for diagnostic, monitoring, and management practices in black women and for future guideline recommendations. Given the heterogeneity among studies, future research should address the relative contributions of biologic, environmental, socioeconomic, and healthcare factors to the observed disparities. Furthermore, longitudinal research is required to address patient-pressing complications, including cardiovascular events and mortality rate in black women with polycystic ovary syndrome as a high-risk yet understudied population.”


Source: Jia Zhu, MD1, Laura Brigitte Leen Wittemans, PhD, Yee-Ming Chan, MD, PhD et al. OR17-3: A Genetically Defined Male Counterpart of Polycystic Ovary Syndrome: Evidence for Ovarian-Independent Pathogenesis. Boston Boston Children’s Hospital, University of Oxford, Oxford, United Kingdom. Presented at ENDO2021 conference, March 2021.
Kazemi M, Kim JY, Parry SA, Azziz R, Lujan ME. Disparities in cardio metabolic risk between black and white women with polycystic ovary syndrome: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020 Dec 13:S0002-9378(20)31395-8. doi: 10.1016/j.ajog.2020.12.019.