D. Exogenous Hormones
1. Androgen Excess
Production of LH and FSH is inhibited by negative feedback from estrogens and androgens at both the hypothalamus and pituitary levels. Androgen excess may induce a hypogonadal state whether from exogenous sources or endogenous production, such as a metabolic abnormality or an androgen- producing tumor. Congenital adrenal hyperplasia is the most common cause of endogenous androgen excess. A congenital deficiency of 21-hydroxylase is the most common cause of the five enzyme defects responsible for this syndrome. A deficiency of 21-hydroxylase results in a decrease in cortisone synthesis, which leads to increased pituitary production of adrenocorticotropic hormone (ACTH). Elevated levels of ACTH result in hyperstimulation of the adrenal gland and in increased production of adrenal androgens. Excess androgens feed back to the pituitary, inhibiting the production and secretion of gonadotropins and leading to hypogonadism. Short stature and precocious puberty develop in these patients. As a result of androgen stimulation, premature enlargement of the penis may occur-, however, because of a lack of gonadotropin stimulation, the testes remain underdeveloped. Basal plasma 17-hydroxyprogesterone levels are often elevated 50 to 200 times above normal levels. In addition, elevated urinary 17-ketosteroid and pregnanetriol levels may occur. Glucocorticoid therapy results in a reduction of ACTH levels, which induces a decrease in peripheral
testosterone, thus stimulating endogenous gonadotropin secretion.
Hypogonadotropic hypogonadism has also been identified after the use of
anabolic steroids by athletes. This condition is usually reversible after medications are discontinued, but permanent suppression of gonadotropin may occur.
2. Estrogen Excess
Pituitary gonadotropin secretion is suppressed by peripheral estrogens. A state of secondary testicular failure may be induced by estrogen-secreting tumors in the adrenal cortex or in the testis. Testicular Sertoli cell tumors or interstitial cell tumors may produce estrogen. Excess peripheral estrogens may also result from hepatic dysfunction. Peripheral adipose tissue converts androgen into estrogen. Elevated estrogen levels have been identified in morbidly obese patients. Impotence, gynecomastia, and testicular atrophy may result from estrogen excess. Hormonal studies demonstrate low levels of FSH, LH, and
testosterone in the presence of elevated estrogens. Treatment is directed at the underlying condition.
3. Prolactin Excess
Impotence and infertility have been associated with hyperprolactinemia. In patients with pituitary adenomas, prolactin levels are elevated and gonadotropins and testosterone levels are depressed. The majority of patients with hyperprolactinemia, however, demonstrate mild elevations and investigations reveal no evidence of pituitary tumors. These patients are classified as having idiopathic hyperprolactinemia which may be caused by microadenomas that are too small to be detected by current imaging techniques. Hypoglycemia, hyperaminoacidemia, and dopaminergic antagonists and agonists, as well as other neurotransmitters, stimulate prolactin release. Pathologic stimuli include chronic renal failure, cirrhosis, intercostal nerve stimulation, and pituitary and hypothalamic tumors. Gynecomastia and galactorrhea are uncommon findings in men. Although most women present with microadenomas, most men presenting with prolactinomas have macroadenomas (≥1.0 cm). Patients who have persistent elevation of prolactin should undergo a CT scan or a MRI study of the head. Bromocriptine, cabergoline, surgery, and radiation therapy have been used for the treatment of macroadenomas. Bromocriptine therapy alone is usually successful for the treatment of microadenomas.