Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (P<0.001) and free testosterone (P<0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (P<0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

Cushing's syndrome presenting as disseminated cutaneous Mycobacterium chelonae infection.

Mycobacterium chelonae infection has not to our knowledge been reported as a complication of endogenous Cushing's syndrome. We describe a patient who presented with sporotrichoid M. chelonae infection and olecranon bursitis whose symptoms did not completely resolve until after bilateral adrenalectomy.

Possible hypothalamic impotence. Male counterpart to hypothalamic amenorrhea?

Twenty-one men with erectile complaints who were found to have a low level of serum testosterone without a reciprocal elevation of the serum levels of luteinizing hormone were evaluated to identify whether the defect was of hypothalamic or of pituitary origin. Patients underwent a luteinizing hormone (LH)-follicle-stimulating hormone (FSH)-releasing hormone stimulation test that showed a normal but sluggish increase in LH and FSH levels, thus ruling out a pituitary defect and suggesting a suprapituitary abnormality. This was confirmed when, in response to clomiphene, patients had a normal increase in gonadotropin and testosterone levels. Although the basal as well as clomiphene and gonadotropin releasing hormone-stimulated levels of total testosterone and gonadotropins were identical in men less than and more than fifty years old, the elevation of free testosterone levels in response to clomiphene was higher in patients younger than fifty. This suggested that although the primary abnormality found in these patients is altered secretion of gonadotropin hormone-releasing hormone from the hypothalamus, an age-related decline in the responsivity of Leydig cells to LH may make it more manifest in older patients. Elevation of testosterone levels from a subnormal to a normal range in response to clomiphene administered for seven days suggests that the defect is functional and reversible and that the drug may be useful in treatment of sexual dysfunction in this group of patients.

Surgically incurable well-differentiated thyroid carcinoma. Prognostic factors and results of therapy.

A series of 97 consecutive patients with well-differentiated thyroid carcinoma treated between 1941 and 1970 presented with distant metastatic disease or extensive nonresectable local neck disease or had residual carcinoma after thyroid resection. Men 40 years of age or younger and women 50 years of age or younger were considered at low risk for dying of disease; older patients were considered at high risk for dying of disease. Of 17 patients with distant metastatic carcinoma, 40% of younger patients in the low-risk group and 92% of older patients in the high-risk group died. Of 80 patients with unresectable or residual local neck cancer, only 13% of younger patients but 71% of older patients died. Survival related better to risk group classification as defined by age and sex than to any details of disease presentation or management. Treatment was far more successful in patients in the low-risk group.