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A New Contributing Factor to Polycystic Ovary Syndrome: The Genetic Variant of Luteinizing Hormone¹

Department of Obstetrics and Gynecology, University of Oulu (J.S.T., R.K.), 90220 Oulu, Finland; the Department of Obstetrics and Gynecology, Dijkzigt Academic Hospital and Erasmus University (B.C.J.M.F.), 3015 GD Rotterdam, The Netherlands; Reproductive Endocrine Unit, Massachusetts General Hospital (A.E.T.), Boston, Massachusetts 02114; the Department of Medicine, School of Postgraduate Medicine, Keele University (R.N.C., M.R.), Hartshill, Stoke-on-Trent, United Kingdom ST4 6QG; the Department of Reproductive Science and Medicine, Imperial College School of Medicine, St. Mary’s Hospital (D.W., S.F.), London, United Kingdom; and the Departments of Obstetrics and Gynecology (L.A.), Biotechnology (K.S.I.P.), and Physiology (I.T.H.), University of Turku, 20520 Turku, Finland

Address all correspondence and requests for reprints to: Dr. Juha S. Tapanainen, Department of Obstetrics and Gynecology, Oulu University Hospital, FIN-90220 Oulu, Finland. E-mail: juha.tapanainen{at}oulu.fi

Although the etiology of polycystic ovary syndrome (PCOS) is still unclear, LH is considered to play a central role in its pathogenesis. An immunologically anomalous form of LH, with two point mutations in the LH_ß gene, has been recently described. This genetic variant of LH (v-LH), of wide geographic distribution, is functionally different from wild-type (wt) LH. To assess the role of the v-LH in PCOS, we analyzed its frequency in groups of PCOS patients from Finland, The Netherlands, the United Kingdom, and the United States. The LH status was determined by two immunofluorometric assays from a total of 1466 subjects. The carrier frequency of the v-LH allele in the whole study population was 18.5%, being highest (28.9%) in Finland and lowest (11.2%) in The Netherlands. In the individual countries, the frequency of v-LH was similar in obese and nonobese controls, but in The Netherlands and Finland, it was 5- to 7-fold lower in obese PCOS subjects compared with that in the other groups (2–4.5% vs. 10.3–33.3%; P < 0.05). A similar tendency 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 women with PCOS suggests that it is compatible with fertility. The similar frequency 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 this finding between patients with apparently similar diagnostic criteria emphasizes the multifactorial nature of this syndrome, and that its pathogenesis may vary according to the genetic background. Although the definitive role of v-LH in PCOS remains to be proven, its determination may improve the prediction of risk of PCOS, especially in obese women.

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