From the Guidelines
Antiandrogenic side effects include a range of symptoms such as weight gain, obesity, diabetes, cardiovascular disease, breast enlargement and/or tenderness, sexual problems, emotional changes, osteoporosis, loss of muscle strength and mass, anemia, and cognitive changes, as reported in the 2010 American Cancer Society guideline for the early detection of prostate cancer 1.
Common Side Effects
The most common side effects of antiandrogenic medications are:
- Weight gain, obesity, and diabetes
- Cardiovascular disease
- Breast enlargement and/or tenderness
- Sexual problems, including diminished sex drive and erectile dysfunction
- Emotional changes, including anger, sadness, and fatigue
- Osteoporosis
- Loss of muscle strength and mass
- Anemia
- Cognitive changes, such as impaired thought processes and memory loss These side effects are typically dose-dependent and may be reversible upon discontinuation of the medication, as noted in the 2004 American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer 1.
Medications with Antiandrogenic Properties
Medications with antiandrogenic properties include:
- Finasteride (5mg daily for BPH, 1mg daily for hair loss)
- Spironolactone (25-200mg daily)
- Cyproterone acetate (50-300mg daily)
- GnRH agonists like leuprolide
Severity and Reversibility
The severity of antiandrogenic side effects varies among individuals based on factors like age, overall health, and specific medication used, as discussed in the 2013 ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of prostate cancer 1. These side effects occur because androgens regulate numerous physiological processes beyond just reproductive functions, including muscle mass maintenance, bone density, fat distribution, and mood regulation. When androgen activity is suppressed, these various systems can be affected, resulting in the observed side effects.
Monitoring and Management
Patients should be monitored for these side effects, particularly when starting treatment or adjusting dosages, to minimize the risk of morbidity, mortality, and decreased quality of life. The most recent and highest quality study, the 2013 ESMO clinical practice guidelines, recommends considering the possible minimal survival benefit together with the cost and toxicity of the additional anti-androgen, and suggests that first-line hormonal management of metastatic prostate cancer should be based on chemical or surgical castration only 1.
From the FDA Drug Label
Based on findings in animal reproduction studies and its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 130 days after the final dose of bicalutamide tablets Antiandrogen therapy may cause morphological changes in spermatozoa Based on animal studies, bicalutamide can lead to inhibition of spermatogenesis and may impair fertility in males of reproductive potential. Adverse reactions considered possibly related to bicalutamide by investigators included gynecomastia (6/14,43%), central precocious puberty (2/14%), breast tenderness (2/14%), breast pain (1/14,7%)
The antiandrogenic (hormone blocking) side effects of bicalutamide include:
- Gynecomastia (breast growth in men)
- Central precocious puberty (early onset of puberty)
- Breast tenderness and breast pain
- Morphological changes in spermatozoa (changes in sperm shape)
- Inhibition of spermatogenesis (reduced sperm production)
- Impaired fertility in males of reproductive potential 2, 2, 2
From the Research
Antiandrogenic Side Effects
The antiandrogenic side effects of hormone blocking therapies can be significant and varied. Some of the common side effects include:
- Decreases in bone mineral density 3
- Metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance 3
- Decreased libido and sexual dysfunction 3
- Hot flashes 3
- Gynecomastia 3
- Reduced testicle size 3
- Anemia 3
- Fatigue 3
- Diarrhea, as seen in patients taking flutamide 4
Comparison of Antiandrogenic Effects
A study comparing the anti-androgenic effects of cyproterone acetate and spironolactone in transgender women found that cyproterone acetate had a higher testosterone suppression efficacy than spironolactone 5. However, cyproterone acetate was also associated with serious adverse effects such as drug-induced liver injury and asymptomatic hyperprolactinemia 5.
Strategies to Mitigate Side Effects
Several strategies have been found to be effective in mitigating the side effects of antiandrogen therapy, including:
- Bisphosphonates, denosumab, and selective estrogen receptor modulators to prevent bone loss 3
- Exercise, diet, and metformin to improve metabolic markers 3
- Tamoxifen and prophylactic radiation to prevent gynecomastia 3
- Resistance and aerobic exercise to prevent muscle loss 3
- Venlafaxine, medroxyprogesterone, cyproterone acetate, and gabapentin to prevent hot flashes 3