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Oxybutynin for Hot Flashes Due to Androgen Deprivation in Men

To the Editor:

Nonhormonal treatments used for menopausal hot flashes in women have generally been found to have limited efficacy against hot flashes induced by androgen deprivation for the treatment of prostate cancer in men. Gabapentin and venlafaxine have been found to have limited efficacy.1 Megestrol acetate, although modestly effective,2 can have hormonal side effects; it has also been associated with decreases in levels of prostate-specific antigen (PSA) after withdrawal that suggest stimulation of tumor growth by the drug3 and, when the drug is used to treat cachexia, it has been associated with rapid growth of metastatic prostate cancer.4 Oxybutynin is effective for refractory hot flashes in women; in one randomized trial, 73% of women who took oxybutynin reported an improvement in symptoms, as compared with 26% of women who took placebo.5

A 65-year-old physician had a PSA-only recurrence of prostate cancer, detected after radical prostatectomy. He had been taking gabapentin (300 mg three times a day) for neuropathic pain, which he continued. He began neoadjuvant and concurrent treatment with depot leuprolide (22.5 mg every 3 months) and bicalutamide (50 mg daily for 6 months), with radiotherapy planned to start after 3 months.

After 2 weeks, he had abrupt onset of nightly drenching hot flashes that occurred every 20 to 30 minutes beginning at 2:30 a.m. The hot flashes were bothersome and intrusive and prevented sleep. The addition of extended-release venlafaxine (75 mg) did not help, nor did increasing the dose of gabapentin to 900 mg at night and 1500 mg a day in total. After more than 21 days of treatment with combined venlafaxine–gabapentin without benefit, oxybutynin (5 mg twice a day) provided relief from the sweating within 2 hours and allowed the patient to sleep through the night. He continued taking the oxybutynin (1.25 to 2.5 mg twice a day) for 40 days and had only transient hourly body warmth, which was far less intrusive than the hot flashes. He tapered and stopped the gabapentin and venlafaxine without a change in the control of his hot flashes. When he stopped taking oxybutynin because of insomnia, dry mouth, and the restless legs syndrome, the hot flashes returned; he restarted treatment with oxybutynin at 2.5 mg twice a day, and relief occurred within hours. The insomnia was managed with intermittent zolpidem treatment.

A recent randomized trial of three antimuscarinic drugs to treat female urge incontinence — oxybutynin, tolterodine, and trospium chloride — showed similar efficacy of all three drugs, but oxybutynin caused more side effects, including dry mouth and insomnia, than the other two drugs. We hope that this case report of successful treatment of refractory hot flashes in a man undergoing androgen deprivation for treatment of prostate cancer will stimulate interest in the oxybutynin class of drugs for hot flashes in men.

Thomas J. Smith, M.D.
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD

Charles L. Loprinzi, M.D.
Mayo Clinic Comprehensive Cancer Center, Rochester, MN

Curtiland Deville, M.D.
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

  1. 1. Loprinzi CL, Dueck AC, Khoyratty BS, et al. A phase III randomized, double-blind, placebo-controlled trial of gabapentin in the management of hot flashes in men (N00CB). Ann Oncol 2009;20:542549.

  2. 2. Loprinzi CL, Michalak JC, Quella SK, et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med 1994;331:347352.

  3. 3. Burch PA, Loprinzi CL. Prostate-specific antigen decline after withdrawal of low-dose megestrol acetate. J Clin Oncol 1999;17:10871088.

  4. 4. Tassinari D, Fochessati F, Panzini I, Poggi B, Sartori S, Ravaioli A. Rapid progression of advanced “hormone-resistant” prostate cancer during palliative treatment with progestins for cancer cachexia. J Pain Symptom Manage 2003;25:481484.

  5. 5. Simon JA, Gaines T, LaGuardia KD. Extended-release oxybutynin therapy for vasomotor symptoms in women: a randomized clinical trial. Menopause 2016;23:12141221.

Source: Massachusetts Medical Society: New England Journal of Medicine: Table of Contents