High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction.

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels.

Testicular function in active ankylosing spondylitis. Therapeutic response to human chorionic gonadotrophin.

Testicular function was studied in 22 patients with ankylosing spondylitis (AS) with serum measurements of hormone levels, seminal fluid analysis and testicular reserve test. Results were correlated with disease activity. The abnormal findings were elevated luteinizing hormone (LH), inversion of estradiol/testosterone ratio (E2:T) and diminished testicular reserve for testosterone (T) and slightly increased for estradiol (E2). Nine patients with severe active AS received biweekly 2,500 IU of human chorionic gonadotrophin injections with a resulting increase in E2 serum levels. When the values of E2 reached 40 pg/ml or higher, there was a decrease of the sedimentation rate (p less than 0.05) and a reversal to normal of the E2:T ratio. This was accompanied by an improvement in AS at the 10th week that lasted up to 9 weeks after discontinuation of treatment. Our findings suggest a possible role of sex hormones in the physiopathogenesis of AS and offers a possible therapeutic alternative.

Ovarian function studies in active ankylosing spondylitis in women. Clinical response to estrogen therapy.

Ovarian function was studied in 17 women with active ankylosing spondylitis (AS). Levels of FSH, LH, prolactin and androstenedione were normal in menstruating patients and FSH and LH were elevated in menopausal patients. In menstruating patients with active AS the estradiol levels were lower than in patients with inactive AS and significantly (p less than 0.05) lower than controls. Progesterone levels in menstruating patients were lower (P = NS) than controls. In menopausal patients estrogen levels were lower than their controls (P = NS). There was a significant (p less than 0.05) inverse correlation between the sedimentation rate and the estrogen level. Seven patients accepted oral estrogen therapy (average duration 4 months) and peripheral arthritis subsided within one month, all variables of clinical activity of AS improved and at the end of the study all patients were in functional class I.