Women’s Health Update

by Tori Hudson, ND

Fish Oils

and

Hot Flashes; IBS

and

Probiotics;

Cohosh

and

Fibroids

The Effect of Fish Oils for Hot Flashes/Night

Sweats: This Time, No Go

Hot flashes and/or night sweats, also known as vasomotor symptoms (VMS), affect up to 80% of women during perimenopause/menopause. Hormonal agents and selective serotonin reuptake inhibitors are the most common conventional options. Women also seek alternatives, including a broad array of botanical and nutritional supplements. While botanicals are the most common of these alternatives used for menopause symptoms and dominate the landscape of published research, a shorter list of nutritional supplements have also been researched. Among these are omega-3 fatty acids, specifically ethyl eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oils.

Only two previous small randomized trials have examined the effect of omega-3s for the treatment of VMS.^1,2 This current study was a 12-week, multicenter, randomized, controlled trial studying the efficacy of 1.8 g/day of a fish oil supplement compared with an olive oil in reducing VMS frequency and/or bothersome/severity. Women were also concurrently randomized to aerobic exercise, yoga, or their usual physical activity. The total of 1.8 gm/day of fish oils were given as 1 pill containing 425 mg EPA/100 mg DHA and 90 mg of other omega-3s, three times per day. Women in the yoga group attended a weekly class; women in the exercise groups attended a supervised aerobic exercise class 3 times per week; and women randomized to their usual level of activity followed their customary routines.

The study was conducted at three US sites. Women were aged 40 to 62 and either perimenopausal with no menses for at least 60 days or in postmenopause or had a history of a bilateral oophorectomy, or a history of hysterectomy and a follicle-stimulating hormone level greater than 20 mIU/mL and estradiol levels of 50 pg/mL or less. All women were generally in good health but had to have at least 14 hot flashes/night sweats per week for at least the previous 3 weeks, and VMS being bothersome or severe during at least 4 or more 12-hour blocks of times each week and a stable level of frequency.

Primary outcomes were VMS frequency and level of bothersome VMS daytime, before bed or night time on a scale from 1 to 4. Secondary outcomes included sleep quality, depressive symptoms and anxiety.

After 12 weeks, the reduction in VMS frequency and severity with omega-3 did not differ from placebo. Omega-3 also showed no improvement in sleep or mood.

Comment

: I was surprised to see the lack of effect from this study, given the two previous positive randomized, controlled trials. In the Lucas study, the supportive role of omega-3 fatty acids in the management of VMS was apparent, but perhaps the study group – menopausal women who also scored high for emotional distress – was a key factor in its results. The rates of depression and anxiety in the current study were low, and it is interesting that serotonin mechanisms have been shown to be a factor in VMS and some SSRIs have shown positive effects. Perhaps women with more emotional struggles and who have VMS are more responsive to the omega-3 fatty acids. To punctuate that point, a 2011 single-blind, placebo lead-in study of peri- or postmenopausal women who received 8 weeks of treatment with fish oil at 2 g/day ; (1 g = 840 mg EE and 375 mg DHA) had a significant improvement in hot flashes day and night, and also had a significant response rate for depression.³ Number of hot flashes per day improved significantly from baseline-day and night. Omega-3 fatty acids have been studied with some success as a treatment of major depressive disorder in several but not all studies. It is not known whether the results of the current study would have been different if the study population included women with a greater degree of depression or anxiety along with VMS, but the previous studies indicate that this might be the case.

Cohen L, Joffe H, Guthrie K, et al. Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial. Menopause. 2013;21(4):347–354.

Multistrain

Probiotics

and Irritable Bowel Syndrome

The relationship between the microbiota in the gut and the etiology (cause) of irritable bowel syndrome (IBS) is becoming increasingly clear. IBS is one of the most common gastrointestinal conditions, and more common in women. It is characterized by abdominal discomfort or pain and variable types of other symptoms, including episodic diarrhea and/or constipation, bloating, and even non-gut symptoms such as backache, muscle pains, joint pains, anxiety and mood issues, and fatigue. The use of probiotics has received much interest in that different probiotics species and strains can affect intestinal motility, visceral hypersensitivity, and secretion of immune chemicals and increase anti-inflammatory populations. While clinical trials with probiotics for IBS still yields conflicting results, improved research designs and research quality are warranted. That said, two large meta-analyses of 2008 and 2009 concluded that probiotics may be of benefit in the treatment of IBS. For practitioners of alternative and integrative medicine in particular, probiotics are becoming one of the mainstays of treatment for IBS. The current study supports that practice.

This recent randomized, double-blind, placebo-controlled trial of adult women and men with symptomatic IBS was undertaken for 12 weeks. A total of 152 patients completed the study, with 100 in the probiotic group and 52 in the placebo group. The four species/strains of probiotic were Lactobacillus rhamnosus NCIMB 30174, L. plantarum NCIMB 30173, L. acidophilus NCIMB 30175, and Enterococcus faecium NCIMB 30176. The bacteria were in a water-based suspension of barley extract, with each 50 mL dose containing 10 billion live organisms.

The primary outcome showed a highly significant result in favor of the probiotic. Improvements in individual symptoms of pain and bowel habits were noted, rather than in bloating or quality-of-life issues. The pain symptoms improved in severity from moderate/severe to mild/no symptoms, although the difference was not considered statistically significant. Four weeks after completing the 12-week treatment, the difference in the IBS symptom severity scores between the probiotic and placebo groups were no longer apparent.

Comment

: In the current study, 94% of the patients enrolled had at least moderate to severe symptoms of IBS … indicating that probiotics can help even these folks. The significant improvement in pain scores in the probiotics group is especially relevant given that pain is most often the single most bothersome symptom of IBS.

Multispecies/-strain probiotics are one of the four pillars in my treatment strategies for IBS which include a probiotic combination of 10 billion per day, plus enteric-coated peppermint oil, a fiber supplement, and lifestyle changes (diet and stress reduction). I typically have a first follow-up in 6 to 8 weeks, which most often results in good improvement, with great improvement by 12 weeks. Adjustments can be made accordingly, with some individuals needing fine-tuning on the kind of fiber supplement that best suits them. If they also have reflux, I would avoid the enteric-coated peppermint oil. I do not hesitate to continue the probiotic combination long term.

Sisson G, Ayis S, Sherwood R, Bjarnason I. Randomised clinical trial: a liquid multi-strain probiotic vs placebo in the irritable bowel syndrome – a 12 week double-blind study. Aliment Pharmacol Ther. 2014; 40:51–62.

Black Cohosh Has a Beneficial Effect on Shrinking Uterine Fibroids

An original menopause study, published in 2007, enrolled 244 Chinese women aged 40 to 60 years with menopause symptoms, who were treated with either black cohosh extract, 40 mg/day (n = 122) or tibolone 2.5 mg/day (n = 122), for 3 months.⁴ The current study investigated the subset of women from that study (n = 62) who had at least one uterine fibroid at the onset of the study, and compared the effect of black cohosh extract (n = 34) on fibroid size compared with tibolone (n = 28), using transvaginal ultrasound.

The patients were treated for 12 weeks with iCR or tibolone. Study visits were at entry, 4 weeks, and 12 weeks. Clinical variables, including the Kupperman Index (KI), vital signs, body weight, coexisting diseases, adverse events, and co-existing medications, were recorded. In addition to blood samples for follicle stimulating hormone (FSH), estrogen, standard hematology, and biochemistry and urine samples, transvaginal ultrasound was also performed before onset of study and at the end of treatment.

In the black cohosh group, the median volume of the largest individual fibroid decreased from 1787 mm³ at visit one to 1086 mm³ after 12 weeks. The mean diameter of the largest fibroid per patient significantly decreased during the treatment with a decrease of the total myoma volume of −30.3% on average observed in 24 of the women in the black cohosh group (70.1%) during the 12 weeks. In the tibolone group, the median volume of the largest individual fibroid changed from 1063 mm to 1096 mm after 12 weeks, actually slightly larger. No statistically significant difference was found for the mean diameter of the individual largest fibroid as well, from baseline to 12 weeks. There was a decrease in the myoma volume in 10 of the women in the tibolone group (35.7%), but on average, it increased by +4.7% in the tibolone group.

In summary, the key results were that the percentage of volume change in the black cohosh extract group (−30.3% decrease) was significantly superior to the tibolone group, a 4.7% increase, and the percentage of mean diameter change in the herbal group was significantly superior to tibolone as well. Lastly, the superior response rate of black cohosh 70.1% vs tibolone 35.7% was important.

Comment

: Other questions about the effect of black cohosh on hormone-sensitive tissues might be considered here as well. A 12-month study showed that after treatment with black cohosh extract, no increase in the risk of malignant change of the breast or endometrium was observed.⁵ In another study, black cohosh extract did not increase the risk of tumor recurrent in patients with early endometrial cancer after 24 months of treatment for menopausal symptoms and after surgery.⁶ In another study, 6 months of treatment with black cohosh daily did not cause change in the mammographic density and breast cell proliferation.⁷ And yet another found that isopropanolic black cohosh extract did not increase the risk of breast cancer recurrence.⁸

To my knowledge, the current clinical study analysis is the first of its kind evaluating the effect of iCR on uterine fibroids. I will add this to my eager approach to helping perimenopausal women in particular, decrease their fibroid growth. We now have two recent botanical studies of import for uterine fibroids: this one and the green tea extract study that I wrote in an earlier column.⁹

Xi S, Liske E, Wang S, et al. Effect of isopropanolic Cimicifuga racemosa extract on uterine fibroids in comparison with tibolone among patients of a recent randomized, double blind, parallell-controlled study in Chinese women with menopausal symptoms. Evid Based Complementary Altern Med. 2014;2014.

Notes

1. Lucas M, Asselin G, Merette C, et al. Effects of ethyl-eicosapentaenaoic omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause 2009;16:357–366.

2. Campagnoli C, Abba C, Ambroggio S, et al. Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement. Maturitas 2005;51:127–134

3. Freeman M, HIbbeln J, Silver M, et al. Omega-3 fatty acids for major depressive disorder associated with the menopausal transition: a preliminary open trial. Menopause 2011;18(3):279

4. W. Bai, H.-H. Henneicke-von Zepelin, S. Wang, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic Cimicifuga racemosa, aka black cohosh (iCR) extract was in Chinese women from five hospitals in China, with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas 2007;58(1):31–41)

5. Geller S, Shulman L, van Breemen R, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009;16(6):1156–1166.

6. Li W, Sun N, Chen X, et al. Cimicifuga racemosa for the treatment of menopausal symptoms in patients with eaerly endometrial cancer after operation. Academic Journal of Second Military Medical University 2012;33(5):562–564.

7. Hirschberg A, Edlund M, Svane G, et al. An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women. Menopause 2007;14(1):89–96.

8. Henneicke-von Zepelin H, Meden H, Kostev K, et al. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. International J of Clinical Pharmacology and Therapeutics 2007;45(3):143–154.

9. Roshdy E, Rajaratnam V, Maitra S, et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int J Womens Health. 2013;5:477–486.