Endocrine Abstracts

Lipodystrophy syndromes are rare diseases characterized by deficiency of subcutaneous adipose tissue. This may affect the entire body (generalized lipodystrophy) or large portions of the body (partial lipodystrophy). Decreased body fat leads to both low levels of the adipokine leptin, and severe insulin resistance due to ectopic lipid storage. Reproductive consequences of lipodystrophy stem from two distinct mechanisms. In patients with severe leptin deficiency (usually generalized lipodystrophy), low leptin leads to an energy conservation state, resulting in partial hypogonadotropic hypogonadism. In patients with both generalized and partial forms of lipodystrophy, insulin resistance leads to hyperinsulinemia as a compensatory response. High insulin acts on the ovaries to create a phenotype comparable to polycystic ovary syndrome (PCOS), with ovarian enlargement, hyperandrogenism, and anovulatory cycles. Hyperinsulinemia also may lead to excess production of 11-oxygenated androgens by the adrenal glands by upregulating CYP11B1. As a consequence of both hypogonadotropic hypogonadism and PCOS, fertility is greatly diminished in women with generalized lipodystrophy and is moderately reduced in women with partial lipodystrophy. Leptin replacement ameliorates both hypogonadotropic hypogonadism and insulin resistance with consequent hyperandrogenism and restores fertility in many women with generalized lipodystrophy. However, pregnancies in women with lipodystrophy have high complication rates, including miscarriage in 34-48%, diabetes (either preexisting or gestational) in over 50%, and preeclampsia in 39-45%. For patients with lipodystrophy in need of contraception or hormone replacement, use of oral estrogens, as in combination oral contraceptive pills, is contraindicated due to the risk of severe hypertriglyceridemia that may precipitate acute pancreatitis. Instead, progestin only or non-hormonal contraceptives are preferred, and transdermal estrogen should be used if estrogen replacement is needed.