Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting women of reproductive age group. PCOS affects as many as 15 per cent of women. It has long been known that there is a strong inherited susceptibility to polycystic ovary syndrome. A new study published in PLoS Medicine, titled ‘Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis’ has now identified two genetically distinct subtypes of the disorder based on genetic and medical data of with polycystic ovary syndrome (PCOS).
The research team found two distinct subtypes of PCOS:
- A “reproductive” group, more strongly linked to hormone levels associated with trouble conceiving, and
- A “metabolic” group more strongly associated with obesity and type 2 diabetes.
The study looked at the DNA of women of European descent by clustering clinical, biochemical and genotype data from a previously published PCOS genome wide study called GWAS. They made connections with the genotypes and the phenotypic or physical subtypes of the condition. Out of the 893 women, included in the study, 23% fell into the reproductive category characterized by higher levels of luteinizing hormone (LH), which triggers ovulation; higher levels of sex hormone-binding globulin (SHBG), a protein regulating the ability of testosterone to enter target tissues; relatively low body mass index (BMI), averaging 25; and lower insulin. Another 37 % per cent were found to display traits ascribed to the metabolic group, which was categorized by higher BMI (41 on average), higher glucose and insulin levels, and lower SHBG and LH levels.
The remaining 40% had a greater frequency of gene variants associated with PCOS and no distinguishable pattern.
“We’re starting to make headway on what causes PCOS. It’s very frustrating for patients because it’s poorly understood, and patients often see several physicians before PCOS is diagnosed. Through genetics, we’re beginning to understand the condition and may have specific targeted therapies in the not-too-distant future.”,
Says senior author Andrea Dunaif, MD, chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes, and Bone Disease at Mount Sinai in New York City.
The study also created a separate predictive model was developed to see the subtypes ran in families. The researchers looked at a family-based cohort of 73 women with PCOS and their siblings and found that the subtypes tended to cluster in families. Then, to see if results could be replicated, the study looked at an independent group of 263 ungenotyped women with PCOS and found a similar breakdown; 26 per cent in the reproductive subtype, 39 per cent in the metabolic one, and the rest having no distinguishable pattern.
Symptoms of PCOS
Many women have PCOS but don’t know it. PCOS affects a woman’s ovaries, the reproductive organs that produce estrogen and progesterone — hormones that regulate the menstrual cycle.
In women with PCOS, some of the common symptoms includes:
- Irregular or missing periods
- Elevated androgens (hormones that males typically have in higher levels than women)
- Heavy bleeding
- Thinning scalp hair
- excess hair growth on the body and face
- Weight gain
- Acne
The syndrome is also linked to insulin resistance (when the body can’t use that hormone effectively and blood sugar levels rise), and therefore women with PCOS are at an increased risk of developing type 2 diabetes and heart disease.
How the Findings may Help with Diagnosis in Future
The findings with further studies and research of these subtypes and the genes identified could lead not only to better targeted treatments for PCOS but also to improve the treatment of fertility problems in women with PCOS and associated conditions that they have, such as diabetes.
“Already, knowing that there are the subtypes and the hormones that are most associated with them — which are different than the hormones that we measure now to diagnose PCOS — may show that it’s better to measure LH and SHBG than to do the ovarian ultrasounds, though we have to prove this.”, claims Dunaif.
More Developments Needed
Despite the revealing results, data collected only from women of European descent stands as a limitation to the study. More extensive studies with a wide-ranging population would be more conclusive and the authors of the study have said that research expanding into other populations is currently underway.
More studies in diverse populations with PCOS would help better understand the genetic patterns and whether or not the subtypes exist across different groups.
