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Nonhormonal menopause treatment did not inhibit enzyme related to tamoxifen conversion
WASHINGTON — An in vitro investigation showed that a nonhormonal purified pollen extract did not inhibit the CYP2D6 enzyme involved in tamoxifen conversion to active metabolites, according to a poster presentation at the 25th annual meeting of The North American Menopause Society.
Proven safe and effective in a randomized clinical trial to treat vasomotor symptoms, Relizen (JDS Therapeutics) was recently brought to the United States after being used in Europe for more than 15 years, Steven R. Goldstein, MD, of New York University School of Medicine, told Endocrine Today.
Steven R. Goldstein
Women with breast cancer and taking tamoxifen would not be treated with estrogen to treat vasomotor symptoms, Goldstein said. The selective serotonin reuptake inhibitor paroxetine mesylate (Brisdelle, Noven Therapeutics) also inhibits the CYP2D6 enzyme system and reduces the effects of tamoxifen.
“Tamoxifen produces some of the worst hot flashes women get,” Goldstein said. “You have a situation where patients can’t use estrogen and shouldn’t use Brisdelle. Here’s a product that shows efficacy in vasomotor symptoms and has no effect on CYP2D6.”
In pooled human liver microsomes, Goldstein and colleagues tested a powder mixture of 75% pollen/pistil extract P182 and 25% pollen extract GC Fem (PE-F/S). For reference, the researchers used the known CYP2D6 inhibitor quinidine.
The researchers evaluated six concentrations of each compound, with all reactions performed in triplicate; Relizen concentrations ranged from 1.65 mcg/mL to 400 mcg/mL. Quinidine doses ranged from 2.06 nM to 500 nM. The endpoint sought was conversion of bufuralol to 1-OH-bufuralol, analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).
“The usual human dose of Relizen is approximately 80 mcg/mL, thus the highest test dose corresponds to five times the recommended daily dose,” the researchers wrote.
At all concentrations, the inhibition of CYP2D6 seen with Relizen was negligible and ranged from –6.53% to 10.67%. CYP2D6 inhibition observed with quinidine showed a linear increase with dose and ranged from –7.07% at 2.06 nM to 84.05% at 500 nM.
“Based on the randomized placebo-controlled trial and my anecdotal experience, I think doctors may want to start using the therapy with tamoxifen patients and then extend it to anybody who has vasomotor symptoms but really doesn’t want to be on a pharmaceutical product or an estrogen product or an antidepressant, which is all that’s available right now,” Goldstein said.
The therapy could have tremendous interest among nongynecologists. “One of the reasons why nongynecologists shy away from hormone therapy is because there is a risk for vaginal bleeding. The beauty of this product is it will not cause any,” Goldstein said. — by Allegra Tiver
For more information:
Goldstein SR. Abstract P-9. Presented at: The North American Menopause Society Annual Meeting; Oct. 15-18, 2014; Washington, D.C.
Disclosure: Goldstein reports being a consultant for Cook OBGYN, JDS Therapeutics, Noven, Pfizer, Philips Ultrasound, Shionogi and Teva.