The connective tissue diseases and the overall influence of gender.

The autoimmune diseases are more common in women than men. The actual prevalence ranges from the high of 10 to 15 females for each male for systemic lupus erythematosus to four females for every male with rheumatoid arthritis. Though these diseases are found in the very young and the aged, the high prevalence is observed after puberty in most patients. These diseases vary with regard to severity, and most investigators suspect that the signs and symptoms of these diseases vary with menstrual cycle and change severity during pregnancy. The collagen diseases are devastating to the health of young women. Rheumatoid arthritis occurring at a mean age of 40 years results in debilitating erosive changes in bone with morning stiffness and eventual crippling. Systemic lupus erythematosus, Sjögren's syndrome and others, common to women of the childbearing years, act in several ways to destroy organ systems of the body. Virtually any organ system of the female anatomy can be affected by these illnesses. In the case of lupus, the disease has protean manifestations, such as procoagulation, renal destruction, skin disease, unrelenting arthropathy and arthritis, and encephalopathy (to name only a few). The underlying mechanisms are not known; however, the immune system acts to destroy tissue via immune complex deposition and through the action of cytotoxic lymphocyte activity. There is an association of both clinical signs and autoantibody subpopulations with markers of the HLA-D or MHC II locus on chromosome 6. No constitutive gene for any of the collagen vascular diseases has been identified in the human. Evidence exists to support an altered metabolism of estrogens and androgens in patients with these diseases. Recent data also indicate that increased estrogen levels might initiate autoimmune diseases in many women and men. Estrogen hydroxylation is increased in both men and women with autoimmune diseases like lupus. The mechanisms are unknown, although estrogenic metabolites have been shown to increase B cell differentiation and activate T cells. Moreover, isolated cases of hyperprolactinemia have been observed in association with these hyperestrogenic states, and treatment of hyperprolactinemia has been shown to ameliorate diseases like lupus. Androgen oxidation is also increased in patients with autoimmune disease, but this abnormality has been observed only in patients with lupus, and only women at that. The result is that women with autoimmune diseases like lupus and rheumatoid arthritis have lower plasma androgens than control cases. These data have supported the use of weak androgens, e.g., DHEA, for the treatment of lupus.