Contents 1 Central nervous system 1.1 Hot flashes 1.2 Sexual dysfunction 1.3 Psychiatric conditions 2 Breasts and reproductive system 2.1 Breast changes 2.1.1 Management of breast changes 2.1.2 Male breast cancer 2.2 Lower reproductive system 2.2.1 Male birth defects 3 Skin, fat, and bone 3.1 Skin changes 3.1.1 Sensitivity to light 3.2 Fat distribution 3.3 Bone density and fractures 4 Gastrointestinal system 5 Heart, liver, kidneys, and lungs 5.1 Cardiovascular system 5.1.1 Coagulation 5.2 Kidney function 5.2.1 Anemia 5.3 Liver toxicity 5.4 Lung toxicity 6 Modification of side effects by castration 7 References Central nervous system [ edit ] Hot flashes [ edit ] In the EPC trial, at 7.4 years follow-up, the rate of hot flashes was 9.2% for bicalutamide monotherapy relative to 5.4% for placebo, which was regarded as relatively low. [8] In the LAPC subgroup of the EPC trial, the rate of hot flashes with bicalutamide monotherapy was 13.1% (relative to 50.0% for castration). [8] [9] Sexual dysfunction [ edit ] Bicalutamide may cause sexual dysfunction, including decreased sex drive and erectile dysfunction. [8] However, the rates of these side effects with bicalutamide monotherapy are very low. [8] In the EPC trial, at 7.4 years follow-up, the rates of decreased libido and impotence were only 3.6% and 9.3% in the 150 mg/day bicalutamide monotherapy group relative to 1.2% and 6.5% for placebo, respectively. [8] Similarly, in the trials of 150 mg/day bicalutamide monotherapy for advanced prostate cancer, fewer than 10% of men reported decreased sex drive or reduced erectile function as a side effect. [9] About two-thirds of men in these trials, who had advanced prostate cancer and were of almost invariably advanced age, [10] maintained sexual interest, while sexual function was slightly reduced by 18%. [9] Most men experience sexual dysfunction only moderately or not at all with bicalutamide monotherapy, and the same is true during monotherapy with other NSAAs . [11] Bicalutamide monotherapy at a dosage of 50 mg/day had no effect on nocturnal erections in men with prostate cancer. [12] [13] Similarly to in men, bicalutamide has been associated with minimal or no sexual dysfunction in women. [14] A phase III clinical study of 50 mg/day bicalutamide in conjunction with a combined oral contraceptive in women with severe hirsutism due to polycystic ovary syndrome (PCOS) carefully assessed the side effect of decreased libido and found that the incidence with bicalutamide did not differ from the control group. [14] Minimal rates of reduced sex drive have also been associated with the related NSAA flutamide . [15] [16] These findings are in accordance with the fact that women with complete androgen insensitivity syndrome (CAIS) show normal sexual function in spite of complete loss of androgen receptor (AR) signaling. [17] They are also in accordance with a variety of findings concerning testosterone levels and sexual function in premenopausal women, in which no change in parameters of sexual function, including libido, have been observed in association with increases or decreases in testosterone levels. [17] It appears that testosterone levels within the normal physiological range are not importantly involved in sexual desire or function in women. [18] Psychiatric conditions [ edit ] At 5.3 years follow-up, the incidence of depression was 5.5% for bicalutamide monotherapy relative to 3.0% for placebo in the EPC trial, and the incidence of asthenia (weakness or fatigue) was 10.2% for bicalutamide monotherapy relative to 5.1% for placebo. [19] Rarely, bicalutamide has been associated with hallucinations . [20] This is thought to be secondary to AR antagonism. [20] Breasts and reproductive system [ edit ] Bicalutamide monotherapy and breast side effects in dose-ranging studies in men Study N Dosage Gynecomastia Breast tenderness Ref Tyrrell et al. (1998) a 386 10 mg/day 9% 11% [21] 30 mg/day 26% 42% 50 mg/day 36% 48% 100 mg/day 79% 86% 150 mg/day 78% 89% 200 mg/day 79% 79% Kennealey & Furr (1991) b 210 10 mg/day 29% 38% [22] 30 mg/day 60% 64% 50 mg/day 52% 60% Zanardi et al. (2006) c 66 0 mg/week (controls) 0% 0% [23] [24] [25] 50 mg/week (~7 mg/day) 44% 32% 100 mg/week (~14 mg/day) 50% 64% Footnotes: a = Testosterone levels increased to ~460–610 ng/dL and estradiol levels to ~32–51 pg/mL. b = Testosterone levels increased to ~505–715 ng/dL and estradiol levels to ~32–53 pg/mL. c = Testosterone levels increased to ~540–600 ng/dL and estradiol levels to ~29–34 pg/mL. ... Before (left) and after (right) surgical breast reduction. [32] Tamoxifen , a selective estrogen receptor modulator (SERM) with antiestrogenic actions in breast tissue and estrogenic actions in bone , has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men. [33] [34] Moreover, in contrast to GnRH analogues (which also alleviate bicalutamide-induced gynecomastia), tamoxifen poses minimal risk of accelerated bone loss and osteoporosis. [33] [34] For reasons that are unclear, anastrozole , an aromatase inhibitor (or an inhibitor of estrogen biosynthesis ), has been found to be much less effective in comparison to tamoxifen for treating bicalutamide-induced gynecomastia. [33] [34] A 2015 systematic review of NSAA -induced gynecomastia and breast tenderness concluded that tamoxifen (10–20 mg/day) and radiotherapy could effectively manage the side effect without relevant adverse effects, though with tamoxifen showing superior effectiveness. [35] A 2019 network meta-analysis likewise concluded that tamoxifen was more effective than radiotherapy or anastrozole for preventing bicalutamide-induced gynecomastia. [36] Surgical breast reduction may also be employed to correct bicalutamide-induced gynecomastia. [37] v t e Tamoxifen doses and rates of bicalutamide-induced breast symptoms in men Follow-up timepoint Tamoxifen dosage Placebo 1 mg/day 2.5 mg/day 5 mg/day 10 mg/day 20 mg/day 0 months – 6 months 98% 90% 80% 54% 22% 10% 12 months 99% 95% 84% 56% 38% 19% Notes: Prevention of breast symptoms—specifically gynecomastia and breast pain —induced by 150 mg/day bicalutamide monotherapy with tamoxifen in 282 men with prostate cancer . ... Treatment was well tolerated, although breast pain was recorded in 0/19 (0%), 8/25 (32%) and 14/22 (64%), and gynecomastia in 0/19 (0%), 11/25 (44%) and 11/22 (50%) of subjects on no treatment, Bic 50 or 100 mg, respectively. ^ Zanardi, S.; Puntoni, M.; Maffezzini, M.; Bandelloni, R.; Mori, M.; Argusti, A.; Campodonico, F.; Turbino, L.; Branchi, D.; Montironi, R.; Decensi, A. (2009). ... Reversibility in Testicular Toxicity Assessment . CRC Press. pp. 107–. ISBN 978-0-8493-5980-4 . ^ a b c d e Kolvenbag GJ, Blackledge GR (January 1996). ... Elsevier. 3 December 2010. pp. 44–45. ISBN 978-0-444-53631-0 . Archived from the original on 26 May 2016. ^ Paoletti R (6 December 2012).
