A new contributing factor to polycystic ovary syndrome: The genetic variant of luteinizing hormones

Although the etiology of polycystic ovary syndrome (PCOS) is still unclear, LH is considered to play a central role in its pathogenesis. An immunologi cally anomalous form of LH, with two point mutations in the LHbeta gene, ha s been recently described. This genetic variant of LH (v-LH), of wide geogr aphic distribution, is functionally different from wild-type (wt) LH. To as sess the role of the V-LH in PCOS, we analyzed its frequency in groups of P COS patients from Finland, The Netherlands, the United Kingdom, and the Uni ted States. The LH status was determined by two immunofluorometric assays f rom a total of 1466 subjects. The carrier frequency of the V-LH allele in t he whole study population was 18.5%, being highest (28.9%) in Finland and l owest (11.2%) in The Netherlands. In the individual countries, the frequenc y of v-LH was similar in obese and nonobese controls, but in The Netherland s and Finland, it was 5- to 7-fold lower in obese PCOS subjects compared wi th that in the other groups (2-4.5% us. 10.3-33.3%; P < 0.05). A similar te ndency was found in the United States (5.7% vs. 11.1-25.0%), but not in the United Kingdom. The overall high prevalence of V-LH in healthy women and w omen with PCOS suggests that it is compatible with fertility. The similar f requency of V-LH in healthy nonobese and obese women indicates that obesity per se is not related to the variant. In contrast, the lower frequency of V-LH in obese PCOS patients suggests that v-LH somehow protects obese women from developing symptomatic PCOS. However, the regional differences in thi s finding between patients with apparently similar diagnostic criteria emph asizes the multifactorial nature of this syndrome, and that its pathogenesi s may vary according to the genetic background. Although the definitive rol e of v-LH in PCOS remains to be proven, its determination may improve the p rediction of risk of PCOS, especially in obese women.