Bicalutamide gynecomastia

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Bicalutamide 50 mg/day Gynecomastia Hot flushes Gastrointestinal disturbances (diarrhea) Liver function test abnormalities Breast tenderness... 

The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. 

Antiandrogens include steroids, such as cyprotcronc acetate, and non-steroidal agents, such as bicalutamide, fluta-mide, and nilutamide. They have different endocrine effects and therefore different adverse effects (1). Cyproterone acetate tends to result in a loss of sexual interest and erectile dysfunction, whereas most men experience this only moderately or not at all during nonsteroidal treatment. The most common adverse effects of the non-steroidal agents are gynecomastia and breast... 

The effect of adding finasteride 5 mg/day to high-dose bicalutamide 150 mg/ day has been studied in 41 men with advanced prostate cancer treated over a mean of 3.9 years (21). The serum prostate-specific antigen (PSA) concentration was measured every 2 weeks until disease progression. At the first nadir of PSA, the median fall from baseline was 96.5% a second nadir occurred in 30 of 41 patients, with a median fall of 98.5% from baseline. The median times to each nadir were 3.7 and 5.8 weeks respectively. The median time to treatment failure was 21 months. Adverse effects were minor, including gynecomastia. Sex drive was normal in 17 of 29 men at baseline and in 12 of 24 men at the second PSA nadir, but one-third of the men had spontaneous erections at both times. The authors concluded that finasteride provided additional intracellular androgen blockade when added to bicalutamide. The duration of control was comparable to that achieved with castration, with preserved sexual function in some patients. 

In a series of studies from Italy an attempt was made to determine whether giving anastrozole 1 mg/day and/or tamoxifen 20 mg/day could prevent gynecomastia and breast pain due to bicalutamide 150 mg/day (72). In a 48-week double-blind study tamoxifen reduced the symptoms but anastrozole did not. 

In one case a man taking bicalutamide developed gynecomastia, which proceeded to breast cancer (76). 

Aniiandrogens Flutamide, bicalutamide, nilutamide G+ Gynecomastia. Aniline metabolite of flutamide has caused methemoglobinemia (see p 261). Nilutamide 13-g ingestion resuited in no evidence of toxicity. 

Treatment of prostate cancer with bicalutamide is valuable, but it tends to cause gynecomastia and breast pain. Tamoxifen can be used to attenuate these complications, but there has been some doubt about... 

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