Androgen and Estrogen Production in Elderly Men with Gynecomastia and Testicular Atrophy after Mumps Orchitis*

Abstract

Gynecomastia developed in three men 1-30 yr after the occurrence of testicular atrophy due to mumps orchitis. At the time of study, these men were 63-68 yr of age. In these men the mean plasma production rate of testosterone was 816 microgram/24 h, a value 20% of that found in normal elderly men without gynecomastia. The plasma production rate of androstenedione averaged 1317 microgram/24 h. The mean production rates of 17 beta-estradiol and estrone in these subjects were 33 and 48 microgram/24 h, values comparable to those of normal young men. Extraglandular formation of estrogen from plasma prehormones accounted for all of the 17 beta-estridiol and most of the estrone produced by these elderly men with gynecomastia. Serum gonadotropin concentrations were elevated in these men, probably because plasma testosterone production rates were decreased. These findings are consistent with the view that the capacity of Leydig cells to secrete testosterone was impaired after mumps orchitis in these subjects, but the capacity to form estrogen was not similarly impaired, since most estrogen is formed in extraglandular sites. Thus, the impairment in Leydig cell testosterone secretion after mumps orchitis together with the normal increase in extraglandular aromatization that accompanies aging bring about a striking reduction in the ratio of testosterone to estrogen production rates, and gynecomastia may result.

Susceptibility of Human Testis to Human Immunodeficiency Virus-1 Infection in Situ and in Vitro

“…However, under our culture conditions, infection of the testis did not modify testosterone secretion, which is in line with our previous data demonstrating that isolated human Leydig cells are not infected by HIV-1 strains in vitro. 55 This contrasts with the situation prevailing in mumps patients as the decrease in circulating testosterone production also observed in these men 56 was associated with a permissivity of human Leydig cells for the mumps virus and a marked reduction of testosterone production in vitro. 57 In conclusion, our results reveal that the testis can sustain productive infection by HIV-1 and that virus-replicating cells within this organ are CD68 ϩ macrophages.…”

Endocrinology of gynaecomastia

“…16 This imbalance also occurs in ageing men, although this is due to a combination of reduced testicular function and increased aromatase activity in the greater mass of adipose tissue leading to increased oestrogen production. The effective oestrogen/androgen ratio rises irrespective of whether serum oestrogen increases, and may result in gynaecomastia in the elderly.…”

“…Pain is less common with breast cancer than with gynaecomastia, which may explain the delayed presentation of breast cancer in men. 60 Hypogonadism due to Klinefelter's syndrome or mumps orchitis is known to be a risk factor for breast carcinoma, 16,61,62 but it is uncertain whether there is an increased cancer risk in men with gynaecomastia due to other conditions. Evidence is emerging, however, which implicates chronic hyperoestrogenaemia, hyperprolactinaemia and/or hypoandrogenaemia with the development of breast carcinoma.…”

Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor.

“…Relative estrogen excess occurs when the synthesis or action of androgen is impaired but estrogen production is maintained at or near normal (as occurs in testicular regression or in testicular failure when testicular androgen production ceases but the formation of estrogens from adrenal androgens is unimpaired (3,4] The mechanism by which androgen inhibits estrogen action is unknown. Evidence has been developed in the MCF7 cell line that 17,3-hydroxy-5a-androstan-3-one (dihydrotestosterone)' functions as an antiestrogen by binding to the estrogen receptor itself and like certain other antiestrogens, that dihydrotestosterone can act as a weak estrogen in high concentration (10).…”

“…Extraglandular estradiol formation takes place by two mechanisms, one from the direct conversion of testosterone to estradiol and the other from androgens of adrenal origin by the sequence of androstenedione -estrone -estradiol. The function of estradiol in normal men is unknown, but feminization, commonly manifested by gynecomastia, ensues under conditions of relative or absolute estrogen excess (2).Relative estrogen excess occurs when the synthesis or action of androgen is impaired but estrogen production is maintained at or near normal (as occurs in testicular regression or in testicular failure when testicular androgen production ceases but the formation of estrogens from adrenal androgens is unimpaired (3,4] The mechanism by which androgen inhibits estrogen action is unknown. Evidence has been developed in the MCF7 cell line that 17,3-hydroxy-5a-androstan-3-one (dihydrotestosterone)' functions as an antiestrogen by binding to the estrogen receptor itself and like certain other antiestrogens, that dihydrotestosterone can act as a weak estrogen in high concentration (10).…”