NATIONAL HARBOR, MD. – Relizen, a nonhormonal purified pollen extract with demonstrated efficacy in treating vasomotor symptoms of menopause, had negligible effects on the CYP2D6 enzyme at five times the recommended daily dose, according to a poster presentation.
Because tamoxifen is metabolized into endoxifen, the active metabolite in the CYP2D6 enzyme, the findings could mean women with severe hot flashes who are taking tamoxifen now have a viable treatment option that won’t increase their risk of death from breast cancer.
Dr. Steven R. Goldstein
“Tamoxifen creates some of the worst hot flashes we will ever see,” Dr. Steven R. Goldstein, professor of obstetrics and gynecology at New York University, said in an interview at this year’s annual meeting of the North American Menopause Society. Even so, because systemic estrogen is contraindicated in women using either tamoxifen or raloxifene for the treatment or chemoprevention of breast cancer, and questions remain about the safety of phytoestrogens, many of these women forgo the commonly prescribed estrogen-based treatments for menopausal symptoms.
Instead, some physicians will prescribe off-label low doses of antidepressants to treat vasomotor symptoms in this patient population. However, a 2010 population-based cohort study of 2,430 Canadian women taking tamoxifen concurrently with an SSRI showed that the risk of death from breast cancer increased 24%-91% in those taking paroxetine in particular, depending on the increasing overlap of tamoxifen treatment and antidepressant use (BMJ 2010;340:c693 [doi:10.1136/bmj.c693]). Last year, the Food and Drug Administration approved the vasomotor symptoms of menopause as an indication for the SSRI paroxetine (Paxil, Brisdelle), but required Noven, the drug’s manufacturer, to state paroxetine’s countering effect on tamoxifen’s efficacy.
Until now, according to Dr. Goldstein, fears over estrogen and SSRI’s potential ill-effects have meant that many women have chosen to “tough it out” when it comes to hot flashes, night sweats, and other symptoms.
The importance of his study, he said, is that because Relizen (Sérélyspharma, France), a powdered, pollen cytoplasmic extract harvested in southern Sweden, doesn’t affect the CYP enzyme system, it’s safe to give to tamoxifen patients. “It is the only nonpharmacologic product that I have ever been aware of that has a double-blind, randomized, placebo-controlled, parallel study showing that it reduces vasomotor symptoms and improves quality of life in menopausal women,” Dr. Goldstein said.
In an in vitro study of Relizen’s effect on the isoenzyme CYP2D6 in pooled human liver microsomes, Dr. Goldstein and his colleagues tested the supplement against quinidine, a known CYP2D6 inhibitor. The end point was the conversion of bufuralol to 1-OH-bufuralol in the CYP enzyme system. Six concentrations of each compound were tested, with all reactions being performed in triplicate. The Relizen concentrations ranged from 1.65 mcg/mL to 400 mcg/mL, five times the Relizen recommended daily dose of 80 mcg/mL. The quinidine concentrations ranged from 2.06 nM to 500 nM.
The study compound’s inhibition of CYP2D6 was negligible, ranging from –6.53% to 10.67%, compared with quinidine’s CYP2D6 linear dose-related increase from –7.07% at 2.06 nM to 84.05% at 500 nM.
Relizen’s apparent clinical utility in women at high risk of death from breast cancer is the “low-hanging fruit,” Dr. Goldstein said. “The tamoxifen patient has no other place to go. But if a woman is 51 years old and she comes to me and says she has hot flashes, now I have multiple options. I can give her hormones, I can give her 7.5 mg of paroxetine, or I can give her Relizen. This is just another arrow in my quiver.”
In the placebo-controlled study of Relizen, 65% of the active treatment group of 32 peri- and postmenopausal women reported decreased vasomotor symptoms by the end of the 12 week trial, compared with 38% of the placebo group (Climacteric 2005; 8:162-70).
“I know [Relizen] is effective, and it’s tested against placebo,” Dr. Goldstein said. “But is it as strong as estrogen? I have no clue. A head-to-head trial is not going to happen.”
Relizen has been widely available in Europe under a variety of names, including Femal, since 1999, and has had no reported adverse effects, according to the manufacturer. JDS Pharmaceuticals (Noven) began distributing the supplement in the United States earlier this year.
Dr. Goldstein is a paid consultant for JDS Pharmaceuticals, a division of Noven. The study was sponsored by the supplement manufacturer, Sérélyspharma(France). JDS Pharmaceuticals (Noven) is the licensed distributor of Relizen in the United States.