Nilutamide

Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer. It has also been studied as a component of feminizing hormone therapy for transgender women and to treat acne and seborrhea in women. It is taken by mouth. Side effects in men include breast tenderness and enlargement, feminization, sexual dysfunction, and hot flashes. Nausea, vomiting, visual disturbances, alcohol intolerance, elevated liver enzymes, and lung disease can occur in both sexes. Rarely, nilutamide can cause respiratory failure and liver damage. These unfavorable side effects, along with a number of associated cases of death, have limited the use of nilutamide. Nilutamide acts as a selective antagonist of the androgen receptor (AR), preventing the effects of androgens like testosterone and dihydrotestosterone (DHT) in the body. Because most prostate cancer cells rely on these hormones for growth and survival, nilutamide can slow the progression of prostate cancer and extend life in men with the disease. Nilutamide was discovered in 1977 and was first introduced for medical use in 1987. It became available in the United States in 1996. The drug has largely been replaced by newer and improved NSAAs, namely bicalutamide and enzalutamide, due to their better efficacy, tolerability, and safety, and is now rarely used. Nilutamide is used in prostate cancer in combination with a gonadotropin-releasing hormone (GnRH) analogue at a dosage of 300 mg/day (150 mg twice daily) for the first 4 weeks of treatment, and 150 mg/day thereafter. It is not indicated as a monotherapy in prostate cancer. Only one small non-comparative study has assessed nilutamide as a monotherapy in prostate cancer. Nilutamide has been used to prevent the effects of the testosterone flare at the start of GnRH agonist therapy in men with prostate cancer. Nilutamide has been studied for use as a component of feminizing hormone therapy for transgender women. It has been assessed in at least five small clinical studies for this purpose in treatment-naive subjects. In these studies, nilutamide monotherapy at a dosage of 300 mg/day, induced observable signs of clinical feminization in young transgender women (age range 19–33 years) within 8 weeks, including breast development, decreased body hair (though not facial hair), decreased morning erections and sex drive, and positive psychological and emotional changes. Signs of breast development occurred in all subjects within 6 weeks and were associated with increased nipple sensitivity, and along with decreased hair growth, were the earliest sign of feminization. Nilutamide did not change the size of the prostate gland (which is the same as with high-dosage cyproterone acetate and ethinylestradiol treatment for as long as 18 months), but was found to alter its histology, including increased stromal tissue with a significant reduction in acini and atrophic epithelial cells, indicating glandular atrophy. In addition, readily apparent histological changes were observed in the testes, including a reduction in tubular and interstitial cells.