Four Studies & HRT Position Paper from the North American Menopause Society Conference

At the annual meeting in October, 2017 of the North American Menopause Society (NAMS) in Philadelphia, researchers presented a number of valuable studies for your practice:

Study 1: Women More Likely to Opt Out of Hormone Replacement Therapy and Choose Alternatives

A study, which was the first to examine women’s beliefs and attitudes toward menopause, outlined an interesting dichotomy – though hormone replacement therapy (HRT) is available for the treatment of hot flashes, a significant number of patients remain skeptical. They prefer alternative options, including exercise, diet, herbal supplements, acupuncture, or meditation.

Though hot flashes, including night sweats, affect up to 80% of all menopausal women in the US, women are less willing to use hormone therapy to relieve symptoms. This has resulted in a decreased number of prescriptions and hormone usage.

Though women agree hormone therapy could relieve hot flashes, they preferred to seek out alternative treatments. “Our findings suggest that women are less willing to use the most empirically validated treatment for hot flashes than other alternative treatment options,” says Dr. Terry Gibbs, lead author of the study from Promedica Physicians in Sylvania, Ohio. “Also, their confidence in successful treatment outcomes was not greater for hormone therapy than the other options.”

While those in integrative medicine may find these study results encouraging, as they express a wider acceptance for the use of botanical and supplements and mind-body medicine, the study authors, who are in favor of HRT, believe that education gaps among physicians may be the reason for the reluctance to use HRT.  Here are the results of a survey of 1,087 physicians, nurse practitioners (NPs) and physicians assistants (PAs) who were given the details of a new medical education program about the empirical evidence that supports HRT: 

Participants were asked a series of questions before and after reviewing the educational program to identify knowledge gaps relative to hormone safety and determine if additional education would help to overcome misperceptions. Among physicians, the average percentage of participants who correctly answered test questions related to outcomes of the WHI trials was 57% pre-activity and 70% post-activity; for NPs, the average percentage answering correctly was 49% pre-activity and 68% post-activity; and for PAs, 52% and 70% respectively.

“We had expected physicians to demonstrate better results in both the pre- and post-activity tests. As a result of the added education there was improvement in some key areas including the newer analysis of the WHI showing different risks depending on age of starting HT,” says Dr. JoAnn Pinkerton, NAMS executive director. This study tells us that there remains an unmet need to educate women about the safety and effectiveness of hormone therapy for most symptomatic women. The benefits go beyond the relief of hot flashes and include improvement in night sweats, sleep disruption, prevention of bone loss, and fewer heart events,” says Pinkerton.

Editor’s Note: At this year’s NAMS conference the organization presented a position paper that outlines new practitioner guidelines for HRT. Click here for the online version.

Study 2: Impact of microbiota on use and effects of isoflavones in the relief of climacteric symptoms and additional benefits in menopausal women

The efficacy of equol in several health benefits and especially in menopause related problems is the objective of this review. In addition to the hormonal effect that directly affects the relief of menopausal symptoms, isoflavones have been associated with beneficial effects on human health, mainly because of its antioxidant capacity, including reduction of the risk of cardiovascular disease, lower risk of cancer and reduces the risk of osteoporosis. Phytoestrogen therapy is well accepted among women who cannot or do not wish to use hormone therapy and demonstrate scientific evidence that it can effectively be an alternative treatment for menopausal women.

This review examined the efficacy of isoflavones therapy for menopause. While not an exhaustive review, it focused on those therapies cited most frequently in recent recommendations or guidelines from national organizations, systematic reviews, and meta-analyses.

Results: The potential benefits of isoflavones on menopausal women’s health have attracted great attention, not only because it is an alternative to hormonal therapy in the improvement of climacteric symptoms, but also because it is able to act in the prevention of diseases that is more prevalent in this stage of life, such as cardiovascular disease, breast cancer and osteoporosis. Gut microbiota is essential for the metabolism and subsequent clinical effect of the isoflavones. The functionality of isoflavones depends on their bioavailability and their conversion within the intestinal tract to metabolites more active than the aglycones forms, as equol (metabolite produced from daidzein), for this is important variability of the intestinal microorganisms.

Therefore, supplying suitable equol-producing probiotic bacteria can optimize the estrogenic action of isoflavones and their metabolites, to promote health improvements complementary to the usual relief of climacteric symptoms, as reduced incidence of hormone-dependent and aging-associated diseases such as osteoporosis, cardiovascular diseases and cancer.

Conclusion: The dietary supplements, soy and soy isoflavones have the strongest evidence for being effective in reducing frequency and severity of hot flushes. Dietary soy or soy isoflavones (S-equol-containing supplements) may be recommended for vasomotor symptoms.

Study 3: Clinical efficacy of an ammonium succinate-based dietary supplement in women with menopausal symptoms: a pooled analysis of two randomized, multicenter, double-blinded placebo-controlled clinical trials.

A pooled analysis of data from two randomized, multicenter, double-blinded placebo-controlled clinical trials. Both studies evaluated an ammonium succinate-based daily dietary supplement (AS) versus a daily placebo for a 3-month study duration. The designs of both trials were identical, thus allowing for pooling of demographic and outcome data to carry out outcome analyses. The studies enrolled healthy postmenopausal women (12 months amenorrhea) between 42 and 60 years of effects of study supplement and placebo on vasomotor and psychosomatic climacteric symptoms. Body mass, BMI and waist circumference, levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, leptin, apolipoproteins A1 and B were evaluated as secondary endpoints. All laboratory measurements of both trials were conducted using the same test kits and on the same equipment.

Results: A total of 227 women, aged 42–60 years, were recruited for the two studies with 114 women in the treatment group and 113 women in the placebo group. Analysis of the Greene Climacteric Scale results showed a statistically significant (p<0.05) reduction in 16 out of 21 menopausal symptoms, including hot flashes, night sweats and lack of sex drive, in the treatment group compared to placebo users who showed no such reductions. State-Trait Anxiety Inventory showed that AS supplementation resulted in a significant decrease in anxiety compared to placebo (p<0.0001).

Over the course of the AS treatment and by the end of the study, the patients showed significant (p<0.0001) increase in the levels of estradiol compared to the baseline (from 35.7 to 58.0 pg/ml). Levels of FSH and LH decreased slightly in both groups, without significant differences between the groups. No significant differences were observed in the anthropometric parameters (weight, BMI, waist circumference) in the groups at study initiation; however, analysis of the anthropometric changes demonstrated statistically significant reductions in the weight, BMI and waist circumference changes among AS users. Average leptin levels within the groups did not differ significantly between the baseline and end of the study; however,

by the conclusion of the trial, leptin levels were significantly lower in the Amberen group compared to the placebo group (p=0.027). For those with initial leptin levels above the reference range, levels decreased significantly in the AS group compared to the baseline (from 16.5 to 14.1 ng/ml, p<0.0001) and to placebo (p=0.027). There were no significant differences in levels of apolipoproteins between the two groups.

Conclusion: A daily dietary supplement containing ammonium succinate has been shown to relieve climacteric symptoms in menopausal women and to improve overall quality-of-life. In addition, our study surprisingly shows that users of AS were more likely to show beneficial changes in anthropometric characteristics than placebo users. Further study is needed to characterize longer term use of AS as well as the duration of benefits. Sources of Funding: Supported by Lunada Biomedical, Inc.

Study 4: Effect of Foeniculum vulgare Mill (fennel) on menopausal symptoms in postmenopausal women: a randomized, triple-blind, placebo-controlled trial

In this small trial of 79 Iranian women aged 45 to 60 years, soft capsules containing 100 mg of fennel were administered twice daily for eight weeks. Improvements were compared between the intervention and placebo groups at four, eight, and 10 weeks, with a significant statistical difference documented. In the end, fennel was concluded to be a safe and effective treatment to reduce menopause symptoms without serious side effects.

The study described in the article “Effect of Foeniculum vulgare Mill. (fennel) on menopausal symptoms in postmenopausal women: a randomized, triple-blind, placebo-controlled trial” is one of the first clinical studies to examine the benefits of fennel for managing menopause symptoms, even though it had been previously studied and confirmed to manage premenopause symptoms. The study was completed in Tehran, Iran, where the average age of women at menopause is younger than in the United States: 48.2 years versus 51 years, respectively.

Some of the most common adverse effects of menopause are hot flashes, vaginal dryness, sleep problems, joint and muscular discomfort, exhaustion, irritability, anxiety, and depression. “This small pilot study found that, on the basis of a menopause-rating scale, twice-daily consumption of fennel as a phytoestrogen improved menopause symptoms compared with an unusual minimal effect of placebo,” says Dr. JoAnn Pinkerton, executive director of NAMS. “A larger, longer, randomized study is still needed to help determine its long-term benefits and side effect profile.”