Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the
polycystic ovary syndrome (PCOS) have not been resolved. In addition to certain
enzyme deficiencies causing a PCOS-like state, current evidence indicates altered functions of
5 alpha-reductase and
cytochrome P450c17 alpha in PCOS patients as a group. However, it is not obvious if these are primary or secondary to the abnormal hormonal milieu. The relation of
insulin-like growth factors (IGFs) to PCOS is of particular interest in view of the occurrence of
IGF-II mRNA in the granulosa cells and the ability of
IGF-I to regulate the granulosa cell and thecal-interstitial cell functions. In obese PCOS patients, the levels of
sex hormone binding globulin and IGF-binding protein-1 are subnormal in serum, and fasting increases them. Fasting also suppresses high
insulin and
IGF-I concentrations in the same women.
Growth hormone, regulated by
insulin and probably by
IGF-I, appears to be decreased in PCOS patients. Follicular growth, characteristically arrested in PCOS, is regulated by
growth hormone to some extent, and
growth hormone treatment has been found to improve the ovarian response to
gonadotropins in some but not all anovulatory patients. In addition to the administration of
growth hormone itself, therapeutic measures modulating the
growth hormone-ovarian axis are being studied. High serum
luteinizing hormone levels are typical of PCOS. These are often associated with
infertility and
early pregnancy loss. Lowering of the
luteinizing hormone levels by a
gonadotropin-releasing hormone analogue in combination with
gonadotropins improves the outcome of pregnancies as compared with those achieved by
clomiphene citrate. The use of the former regimen in PCOS patients may result in ovarian hyperstimulation. Ovarian
electrocautery has proved to be effective in restoring cyclicity of ovarian function with a concomitant fall in
luteinizing hormone and
androgen levels. Interestingly, an increase in serum insulin secretion has been noted. It remains to be elucidated if this
therapy, followed by decreased
luteinizing hormone, is effective in reducing the elevated risk of
miscarriages in women with PCOS.