Polycystic ovary syndrome (PCOS) is a condition that causes irregular menstrual periods and high levels of androgens (male hormones) in women. The high male hormone levels can sometimes cause an increase in facial hair growth, acne, and/or male-pattern hair thinning. The condition occurs in about 4 to 6 percent of women. Some women with PCOS are overweight or obese, and they are at higher than average risk of developing type 2 diabetes. For women with PCOS who want to become pregnant, hormone pills or injections are often needed to help women ovulate. In some cases, weight loss alone can help ovulation. The cause of PCOS is not known and it is thought to be a common, genetic disorder, as are conditions such as asthma and type 2 diabetes. Such common diseases appear to have many causes in which a variety of genes interact with environmental factors to produce disease. Studies in families have demonstrated the heritable nature of PCOS. Large genetic studies have attempted to discover genes that influence whether or not a patient is susceptible to developing PCOS. Recently, a more sophisticated type of genetic testing has been performed providing more clues to the varied causes of PCOS and what genes influence whether or not someone develops this condition or not.
Family studies demonstrate that PCOS is significantly more prevalent among family members than in the general population. Among first-degree female relatives of 93 patients with PCOS, 35% of premenopausal mothers and 40% of sisters were also affected with the disorder. These affection rates are significantly higher than the 4 to 6% observed in the general population. In another study, 115 sisters of 80 women with PCOS were evaluated; of these, 22% met criteria for PCOS. Brothers of women with PCOS also have elevated levels of male hormones.
Efforts to identify genes that influence PCOS susceptibility have largely utilized something called the candidate gene approach, resulting in over 155 publications over the past decade. Despite repeated attempts to identify the genes responsible for this disorder, the PCOS gene(s) remain unknown. Despite many positive studies, no gene has clearly been shown to be the most important in PCOS, and many positive results were not confirmed in subsequent studies. Studies of the genetic causes of PCOS have been hampered by various limitations some of which are challenges inherent to any common genetic disease and others unique to PCOS.
An attractive method of gene discovery for genetic diseases is to use whole-genome approaches that require no prior knowledge or assumption regarding the underlying causes of disease. The main challenge in conducting this type of genetic study that is different than the candidate gene approach is the need to study large numbers of patients, in the thousands. This type of study was performed in Han Chinese PCOS women demonstrating certain gene locations that were associated with PCOS. A subsequent replication study evaluated these gene locations in a European cohort and two of these locations were also associated with a susceptibility to PCOS in the European group.
Methodological flaws have led many to lose faith in PCOS genetics. Improvements in study design as well as a higher number of patients studied and technological advances allowing more in depth genetic evaluations will eventually lead to success. We believe that lessons learned from genetic studies will improve our understanding of this extremely common disorder and allow more effective measures for prevention, diagnosis, and treatment.