Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue

Abstract

This study measures the effect of megestrol acetate (Megace), a progestational antiandrogen, on nuclear and cytosol receptor concentrations in human BPH prostates. Prostatic tissue was obtained at surgery from both untreated patients with BPH and patients pretreated for three to eleven days with 120 to 160 mg of Megace daily; tissues were homogenized and separated into cytosol and crude nuclear fractions. Cytosol and salt extractable nuclear fractions were subjected to saturation analysis with 3H R1881 over the range of 0.5 to 10 nmoles in exchange reactions for 20 hours at 15 degrees C. Cytosol receptor concentration decreased significantly from 32.7 to 8.7 femtomoles per mg protein (P less than 0.05); nuclear receptor also was significantly reduced from 317 to 43.8 femtomoles (fmole) per mg DNA (P less than .001). Plasma testosterone also decreased significantly from 3.65 to 1.01 ng/ml in Megace-treated patients. These effects of Megace on receptor concentration appear to be qualitatively quite different from those reported following castration in animals or following high-dose estrogen therapy in humans. The mechanism of action of Megace in decreasing both cytosol and nuclear androgen receptor concentrations is unknown. It is possible that decrease in receptor concentration is secondary to either the progestational or antiandrogenic effects of Megace. These possibilities are currently under study.

Megestrol Acetate-Induced Symptomatic Hypogonadism in a Male Patient

“…Hyperprolactinemia, which is also associated with hypogonadism, was noted in 19 of 21 subjects with a 150% rise in prolactin levels in the same study. Others have documented that MA decreases the number of androgen receptors (Geller et al) [ 11 ]. However, these hypotheses are still under investigation and the exact mechanism of MA-induced hypogonadism is unknown.…”

Mediators and clinical treatment for cancer cachexia: a systematic review

“…As a synthetic derivative of progesterone, megestrol acetate (MA) has been shown to be well tolerated in patients with advanced malignant diseases, such as cancer 193 and HIV, 194 and has been shown to have a positive effect on improving appetite and gaining body weight 193,194 . It acts primarily to inhibit intracellular androgen action, although it also has a cytotoxic effect at a high concentration 195–197 . In 2005, MA was approved by the Food and Drug Administration (FDA) for treating anorexia, cachexia, or an unexplained significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome.…”

“…193,194 It acts primarily to inhibit intracellular androgen action, although it also has a cytotoxic effect at a high concentration. [195][196][197] In 2005, MA was approved by the Food and Drug Administration (FDA) for treating anorexia, cachexia, or an unexplained significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome. Thus, it was considered as a potential drug for treating cancer cachexia, and several clinical trials were performed to assess this.…”

Seasonal and diurnal changes of prostatic androgen receptor and circulating testosterone in young mature rats

“…Although their animals were kept in the same light/ dark rhythm the times of the maximum and minimum receptor values considerably differed from our findings. Most authors assume that androgen receptors are regulated by circulating androgens (for review see [6,9]; later studies: [1,21]). This theory was deduced from the early events during androgen depletion and repletion.…”