After the 12 week treatment period, the Kupperman index for the red ginseng group significantly reduced from 18.93 to 13.32 compared with the placebo from 15.21 to 15.10. The Menopause Rating Scale score dropped significantly from 12.45 to 8.32 in the ginseng group compared with 10.23 to 9.26 in the placebo group. The hot flash score also reduced significantly in the red ginseng group.

Red ginseng also elicited a significant decrease in total cholesterol from 138.11 to 108.82 compared with the placebo, from 128.52 to 128.03. The drop in LDL was also significant in the red ginseng group compared to placebo but there were no significant differences between the two groups for HDL cholesterol or C-reactive protein. The estrogen levels were not considered to be affected by red ginseng. On the other hand, the carotid intima-media thickness was significantly reduced in the red ginseng group compared with the placebo group.

Commentary: This is not the first randomized, controlled trial using ginseng in menopause symptoms but it is the first double-blind randomized controlled trial to investigate the effect of red ginseng for 12 weeks on menopausal symptoms in postmenopausal women. In the previous trial published in 1999, there were no clear effects on hot flashes but there was an effect on quality of life. In the current study however, there was a clear effect in reducing the menopause symptoms rated on the Kupperman Index and the Menopause Rating Scale, including hot flashes. These are two of the most common research tools in evaluating menopause symptoms.

The positive results of red ginseng for hot flashes in the current study versus the negative results in the previous trial could be explained by the difference in ginseng used. Red ginseng has physiologically active components that are not present in raw white ginseng or the plain Panax ginseng. Another significant difference in the two studies is the 3gmper day of the red ginseng versus the 200 mg of ginseng in the previous study.

Reference

Young Kim S, Kyo Seo S, Mi Choi Y, et al.  Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial.  Menopause 2012;19(4):461-466

While 100 women completed the trial, 19 did not meet the criteria for postmenopause based on FSH levels therefore, data for 81 women were used to analyze the results.

After the 12 weeks of treatment, PGS reduced the number of hot flashes by 4.3 per day and the placebo reduced it by 2.5 per day. Both groups were significantly improved compared to prior to the PGS or the placebo, but the pomegranate group was not statistically significant compared to the placebo group. Interestingly though, 12 weeks after the treatment was stopped, the reduction of hot flashes was significantly different between the PGS and the placebo. The overall total score of the Menopause Rating Scale did decrease in the PGS group from 16.0 to 9.0 at week 12 and from 18.0 to 14.5 in the placebo group. In looking at just the somatic symptoms, the PGS group did have a stronger response that was attributed mainly to an improvement in sleep disorder issues. There was no effect of PGS on hormone levels.

Summary: The not so good news is that pomegranate seed oil in this dose, in this study, did reduce the frequency of hot flashes significantly, but so did the placebo. The better news is that when looking at the overall Menopause Rating Scale sum score, including the severity of hot flashes, there was a trend toward a reduction in menopausal symptoms compared with placebo, although it did not reach the level of significance. In addition, the frequency of sleeping disorders did decrease significantly with the pomegranate seed oil, and after 12 weeks, at the end of the treatment, the difference between PGS and placebo in the reduction of hot flashes was significant. It’s hard to understand the meaning of that, but there is some suggestion of some sustainable, lingering effect of the PGS. Other good news is that they studied it at all, and this is actually the first prospective randomized, placebo-controlled, double-blinded trial that has investigated the effects of pomegranate seed oil on hormone levels in women who are postmenopausal.

Reference

Auerbach L, Rakus J, Bauer C, et al. Pomegranate seed oil in women with menopausal symtpoms: a prospective randomized, placebo-controlled, double-blinded trial. Menopause 2012; 19(4):426-432

As soy isoflavone intake increased, the risk of death decreased. Women at the highest levels of soy isoflavone intake (> 16.3 mg isoflavones/day) had a 54% reduction in risk of death.

Commentary: This is the third epidemiologic study to report no adverse effects of soy foods on the prognosis of breast cancer. Soy foods, which contain isoflavones, a phytoestrogen, show both antiestrogenic and estrogen-like properties. The confusion and controversy has been that many studies have shown that isoflavones may protect against an initial breast cancer but in a very few laboratory studies certain isoflavone components of soy have been able to enhance the proliferation of breast cancer cells in select doses, and have been able to both promote and inhibit mammary tumor growth in rats.

However, in 2009, some clarity began to emerge for breast cancer patients. In breast cancer survivors, one study in Asian women (the Shanghai Breast Cancer Survival Study) and the other in U.S. women (the Life after Cancer Epidemiology study), suggest that soy containing foods do not negatively affect breast cancer prognosis, do not counteract the effect of the breast cancer drug tamoxifen and may in fact provide potential benefits in decreasing risk of recurrence or death from breast cancer.

The current study has explored this issue further, by examining data from a randomized controlled trial, the WHEL study. The results of this study, and the two previous in 2009, should give practitioners and women alike, great reassurance in the safety of soy consumption for women with who have/have had a diagnosis of breast cancer. We no longer need to advise against soy consumption for breast cancer survivors. This is great news given all the potential health benefits of soy for bone health, cardiovascular health and soy as a part of a whole foods and healthy diet.

Reference

Caan B, Natarajan L, Parker B, et al. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 2011;20(5):854-858.

A statistically significant change was reported in the quality of the sleep in the valerian group when compared to the placebo group. The average scored on the sleep scale before valerian was 9.8 and after valerian it was 6.02. The placebo group had an initial average sleep scale score of 11.1 and after placebo, 9.4. Overall, 30% of the women taking valerian and 4% taking placebo reported an improvement in their sleep quality.

Commentary:

Approximately 61% of postmenopausal women have sleep problems, which then of course can lead to other consequences including impaired function, fatigue, depression and reduced quality of life. In addition, hot flushes and night sweats, which affect 75% to 85% of postmenopausal women, can also affect sleep quality.

Valerian is the most commonly used herb for individuals suffering from insomnia and is in the top 10 herbal supplements most commonly used in general. Quite a few studies have been done on valerian and insomnia in the last 20 years but few have studied older adults and no previous studies in postmenopausal women and over a longer period of time such as the current study. Results have been inconsistent and quite varied in the design of the study. Several previous studies have reported improvement in sleep quality in individuals using valerian over time but there are only a few studies with significant improvement in sleep outcomes when compared to placebo. Fortunately, the current study has shown that valerian improves the quality of sleep in postmenopausal women with insomnia, and can add to our treatment options in a much needed area of medicine.

Reference

Taavoni S, Ekbatani N, Kashaniyan M, Haghani H. Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause 2011; 18(9): 951-955.

A systematic review was done to assess the clinical evidence for or against the efficacy of maca for sexual dysfunction. The review included only randomized clinical trials comparing maca to a placebo in men or women with sexual dysfunction. Four randomized controlled trials (RCT) met the inclusion criteria. Two of these trials suggested a positive effect of maca on sexual dysfunction or libido in menopausal women or adult. One other RCT did not show effect of maca in cyclists. The fourth study assessed the effects of maca in men with erectile dysfunction and did show significant effects.

While the evidence is limited, there does appear to be some effectiveness of maca in improving sexual function.

Reference

Shin B, Soo Lee M, Jin Yang E, Lim H, Ernst E. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complementary and Alternative Medicine 2010;10:44

A study of St John’s wort liquid extract showed a statistically decline in hot flashes severity, duration and frequency in the SJW group compared to placebo at week 8.[1]

Another double blind randomized clinical trial demonstrated that after 3 months of treatment, women in the St. John’s wort group reported significantly better quality of life scores, and significantly fewer sleep problems compared to placebo. [2]

About ten years ago, a non placebo controlled, drug monitoring study was conducted in women with menopause symptoms using 900 mg of St. Johns wort for 12 weeks. About three quarters of the women experienced improvement in both the self-rating scale and the physician rating, and significantly improved in psychological and psychosomatic symptoms as well as a feeling of sexual well-being.[3]

The first of three studies using St. John’s wort and black cohosh was published in 1999. This double-blind, randomized, placebo-controlled trial used St. John’s wort and black cohosh made by the makers of Remifemin.[4] The Kupperman index for the combination product decreased from 31.4 to 18.7 compared with a decrease in the placebo group from 30.3 to 22.3. Psychological symptoms also improved significantly in the black cohosh/St. John’s wort combination group.

A double-blind randomized placebo-controlled study was done using a combination trial of black cohosh and St. John’s wort. The mean Menopause Rating Scale score decreased 50% in the treatment group and 19.6% in the placebo group.[5] The Hamilton Depression Rating Scale score decreased 41.8% in the treatment group and 12.7% in the placebo group. In both testing measures the St. John’s wort + black cohosh group was significantly superior to the placebo group.

Another black cohosh/St. John’s wort trial was carried out in peri or postmenopausal Korean women, and was published in 2007.[6] Mean Kupperman index scores at 4 and 12 weeks were significantly lower in the treatment group (P < 0.002). At the end of the study, the average decrease in the Kupperman Index was 20 points in the treatment group and only 8.2 points in the placebo group (P < 0.001). Vaginal dryness and low libido were two symptoms that did not improve, but the average hot flash scores were significantly lower in the black cohosh/St. Johns wort group.

Finally, a study was done in which a combination of black cohosh with or without St. John’s wort was used in 6141 women at 1287 outpatient gynecologists in Germany in a prospective, controlled open-label observational study.[7] The greatest changes occurred with the combination therapy for nervousness/irritability and mood swings, but in the area of depression, there was a reduction in both treatment groups.

St. John’s wort is emerging as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, as a single agent, or in combination with other therapies.

References

[1] Abdali K, Khajehei M, Tabatabaee R. Effect of St. John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2): 326-331.

[2] Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John’s wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Mar-Apr;16(2):307-14.

[3] Grube B, Walper A, Whatley D. St. John’s wort extract: Efficacy for menopasual symptoms of psychological origin. Adv Ther 1999;16:177.

[4] Boblitz N, Schrader E, Henneicke-Von Zepelin H, et al. Benefit of a fixed drug combination containing St. John’s wort and black cohosh for climacteric patients-results of a randomised clinical trial )poster presentation from 6^th Annual Symposium on Complementary Health Care, Exeter, England, December 2-4 1999). Focus Alt Comp Ther 2000;5(1):85-86.

[5] Uebelhack R, Jens-Uwe Blohmer, et al. Black cohosh and St. john’s wort for climacteric complaints. Obstet Gynecol 2006;107:247-255.

[6] Chung D, Kim H, Park K, et al. Black cohosh and St. John’s wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007;48(2):289-294.

[7] Briese V, Stammwitz U, Friede M, et al. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment- Results of a large-scale, controlled, observational study. Maturitas 2007;57:405-414.

Results: The total MRS II score for women while on black cohosh treatment reduced from 17.6 to 13.6, a statistically significant reduction. Symptoms of hot flashes, sweating, sleep problems, and anxiety improved, but vaginal dryness and body aches/pains did not change. Twenty two patients reported adverse events, but none were linked with the black cohosh; 90% of the women reported the tolerability of the black cohosh extract as very good or good.

Commentary: This is one more positive study using black cohosh extract for menopausal symptoms and even more meaningful, women on tamoxifen can have more problematic menopause symptoms and so a significant benefit of black cohosh is especially needed. Readers will also want to be reminded that we do have safety data on black cohosh in breast cancer patients—there is no estrogen in black cohosh, no phytoestrogens in black cohosh, no ability to stimulate breast cancer cells and laboratory data showed that black cohosh inhibited proliferation of estrogen receptor positive breast cancer cells and augmented the anti-estrogen effect when using black cohosh with tamoxifen. Black cohosh is clearly the first choice herb for menopause symptoms in breast cancer patients, and in breast cancer patients on tamoxifen.

Reference:

Rostock M, Fischer J, Mumm A, et al. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints – a prospective observational study. Gynecol Endocrinol. 2011 Jan 13;

This increase risk of breast cancer is similar to the increased risk of having menopause 5 years later than other women. These increased risk are considered small although the additional information from this study had also to do with the cancers being more commonly lymph-node positive (81 vs. 43) , as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths in the Prempro group vs. 31 deaths in the placebo group. On the other hand, the tumors were similar in histology and grade to breast cancers in the placebo group.

Commentary

In summary, use of conjugated equine estrogens and progestin increased the risk of breast cancer incidence after 11 years and the cancers were more commonly node-positive with a suggestion of increased mortality.

This research should not be seen as a rationale to refuse any and all menopausal hormone regimes, but rather, using hormone therapy when needed to treat moderate to severe symptoms of menopause, and use the lowest effective dose for the shortest amount of time necessary. Each woman should be evaluated and have a consultation with a menopause expert practitioner to determine her individual needs, priorities and treatment options and then make an informed choice.

Reference

Chlebowski R, Anderson G, Gass M, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010;304(15):1684-1692.

After 8 weeks, both the hops group and the placebo group had significant improvement in outcome measures compared to the baseline and actually higher average reductions in the placebo group. After 16 weeks however, only the group that was on the hops extract in the second 8 weeks had a reduction in all outcome measures whereas the placebo group in the second 8 weeks had an increase for all outcome measures. Although the overall treatment efficacy of the hops treatment compared with the placebo did not show a significant effect, the time specific uses did indicate significant reductions in the KI and the VAS for the hops group, and a marginal reduction in symptoms for the MRS after 16 weeks.

Commentary: This is the second study on an oral hops extract for menopause symptoms that I am aware of. The German Commission E (the German agency similar to our FDA), has approved hops for mood issues such as anxiety and restlessness, and for sleep disruptions. In the previous randomized, double-blind, placebo-controlled study, 67 menopausal women were given either a placebo or a 100 mcg or 250 mcg standardized hops extract for 12 weeks.[i] At 6 weeks, the 100 mcg dose was significantly superior to placebo, but not after 12 weeks. Even so, there was a more rapid decrease in menopause symptoms scored for both doses of hops extract , especially the hot flush score. The higher dose was not any better than the lower dose. Both the current study and this previous study, used a standardized hops extract at 100 mcg 8-prenylnaringenin. The current study used the lower 100 mcg dose.

This hops standardized extract may provide a useful herb for women suffering from common menopause symptoms such as hot flashes/night sweats. I have been using it in my clinical practice for approximately two years, usually along with one or more of the following: Black cohosh, St. John’s wort, Maca extract or a combination botanical of Dong Quai/burdock root/ wild yam root/ licorice root/motherwort. Hops do contain phytoestrogens and this is the likely mechanism of action.

Reference:

[i] Heyerick A, Vervarcke S, Depypere H, et al. A first prospective, randomized, double blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas 2006;54:164-175.

In the newest of the St. John’s wort studies in perimenopausal/menopausal women, a total of 100 Iranian women with an average age of 50 participated in a randomized, double-blind, placebo-controlled clinical trial comparing St. John’s wort with placebo in the treatment of hot flashes.[1] 50 women received 20 drops three times daily of St. John’s wort extract (Hypericin) that contained hypericin 0.2 mg/mL and 50 women received a placebo of distilled water. The study duration was two months. Clinical exams and interviews were performed at baseline, 4 weeks and 8 weeks. Treatment effectiveness was measured evaluating frequency, duration and severity of hot flashes as the main objective of the study.

In women taking St. John’s wort, the frequency began to decline during the 1^st and 2^nd months, but showed more improvement during the 2^nd month. There was no statistical change in hot flash frequency during the first month of placebo but did improve during the second month. Women who used St. John’s wort showed more improvement in hot flash frequency than placebo. The decline in duration of hot flashes was statistically significant at week 8 and the decline was much more evident in the St. John’s wort group. The severity of hot flashes was relieved in the St. John’s wort group during the 2 months of treatment and was more significant in the second month. Women in the placebo group did not show any significant decrease in severity of hot flashes during the 1^st month, but they did have some improvement during the 2^nd month, but not as great as those women in the St. John’s wort group.

Comments

St. John’s wort has emerged as an important clinical tool in treating perimenopausal/menopausal women—for hot flashes and/or depression and/or mood swings, and/or sleep problems either as an encapsulated standardized extract from 300 mg twice per day to three times per day, or a tincture/liquid extract ½ tsp 2-3 times per day, or in combination with other menopause therapies such as black cohosh, maca extract, kava or others.

Reference

[1] Abdali K, Khajehei M, Tabatabaee R. Effect of St. John’s wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2): 326-331.