Holland and Barrett hit the menopause

Another Week, another charitable day to target, and another set of dubious promotional claims from Holland and Barrett.  This time they have been piggy-backing (somewhat belatedly) on World Menopause Day.  That an event designed to bring some reliable advice to women facing this natural, and unavoidable, transition is used to advertise products of no clear worth seems distasteful to me.

A mail shot improbably entitled, “Beat menopause naturally – save up to 50% on menopause supplements” implies that a range of products can beat the menopause.  The menopause, of course, can’t be beaten; it’s a fact of life.

So much for the advertising strap-line, what of the products that it promotes?

It can be hard to assess claims like these.  The internet records many wild claims, alongside sensible ones, and the medical literature is difficult for the layman.  My usual strategy is to search the Cochrane Library to see what clinical reviews have included these, or similar, products.  This way, I hope to get a balanced view of the literature which takes into account the relative strengths and weaknesses of individual trials.

Let’s start with the soya Isoflavones.  To be fair, these seem to be among the more plausible suggestions.  For instance, Bandolier suggested on the basis of a review published in 1998 by Seidl and Stewart that there is, “some biological plausibility and some epidemiological and clinical evidence” for the use of phytoestrogens in reducing some of the symptoms (loss of bone density and hot flashes particularly).

In 2002 a review published in the International Journal of Gynaecology and Obstetrics by Kang et al. noted that, “The synthetic isoflavone derivative ipriflavone increases bone mineral density in healthy peri- and postmenopausal women with moderate bone mineral densities.”  On the topic of hot flashes they observed, “Although earlier reports have claimed that soy is beneficial for the improvement of vasomotor symptoms, recent data do not support this claim.” [Emphasis mine]

Menopause: a review of botanical dietary supplements, a review published in the American Journal of Medicine in 2005 concluded that, “Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose.” [Emphasis mine]

Another review published in the same year found that there, “were mixed results from trials examining biologically based therapies including phytoestrogens. The largest reasonable quality trial of phytoestrogens in women without breast cancer (n=241) found no differences between groups given two doses of isoflavones or placebo on any outcome.  Nine other trials found no differences between the groups, mixed results, or were considered to be of a poor quality.”  Though three, “fair-quality trials” did report some positive outcomes. [Emphasis mine]

Given that biases and random statistical variation are bound to throw up some false positive results, it would appear that the evidence is not really there.  In fact this review concluded, “There are insufficient data to support the effectiveness of any complementary and alternative therapy for the management of menopausal symptoms.” [Emphasis mine]

Other reviews have concluded that, “the limited evidence … suggests that more research is required“; “the available evidence suggests that phytoestrogens do not improve hot flushes or other menopausal symptoms“.  Finally a methodologically weak review called phytoestrogens, “promising for the treatment of menopausal symptoms”.

This is clearly not sufficient evidence to support claims to “beat menopause”.  It certainly doesn’t seem strong enough to support marketing these pills to women of a certain age.  Perhaps, this intervention may improve moderate bone density is healthy women, but there doesn’t seem to be any real evidence to support the majority of the claims made for this product.  And this intervention, along with the use of black cohosh, probably has the strongest evidence base of all the promoted ‘treatments’.  This doesn’t bode well.

Moving on; “Fish oil concentrate” is certainly cheaper, but I couldn’t find any evidence to suggest that would be any help in moderating the symptoms of menopause. 

Similarly, the Cochrane Library does not provide even a hint that Agnus Castus (dried fruit of Vitex agnus castus) might ameliorate menopausal symptoms (most of the trials listed seem to focus on premenstrual tension syndrome). 

Estrobalance, according to Holland and Barrett is an, “all-Natural Nutritional supplement for women, providing nature’s own estrogens from plants, plus essential vitamins and minerals.”  This appears to be another product following the phytoestrogen theme so, as we have already seen, it comes without sufficient evidence to warrant anything more than, perhaps, further investigation in high quality trials.

The same can be said of “Flash Fighters”, described as, “formulated with soya isoflavones, a natural source of phytoestrogens.”

They contain black cohosh extract, along with Soy Isoflavone.  The Herbal Alternatives for Menopause (HALT study, n= 351) concluded that, “Black cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.” 

Similarly Newton et al. used the same data to compare, “3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo” (n=351) in a year-long study and concluded that, “Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms.” [emphasis mine]

Pockaj et al. concluded in, “Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes” (n= 132) that it, “failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.”

However, I did come across a number of positive trials.  For instance, Frei-Kleiner et al. (n=122) noted that black cohosh was superior, “compared to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index > or =20, but not in the intention-to-treat population as a whole.”  [emphasis mine] This is, at best, somewhat equivocal support.

Oktem et al. (n= 120) claimed that, “Compared with fluoxetine [Prozac], black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck’s Depression Scale.”  However with a 33% drop-out rate in both the black cohosh and fluoxetine arms and no placebo control, the strength of this study is questionable to say the least.

Chung et al. concluded that, “Black cohosh and St. John’s wort combination was found to be effective in alleviating climacteric symptoms” in a, “double-blind randomized, placebo-controlled, multicenter study” of a product called ‘Gynoplus’ which contains both of these ingredients.  However, this was a relatively small study with a total of 89 participants of whom 77 (42 in the Gynoplus group, 35 in the placebo group) completed the 12-week trial.

In 2007 Briese et al. reported on a, “Prospective, controlled open-label observational study”  – so no placebo control – which sought to, “evaluate usage pattern, effectiveness and safety of Black cohosh alone or in fixed combination with St. John’s wort on menopausal symptoms in general clinical practice.”  They concluded that, “The fixed combination of Black cohosh and St. John’s wort was superior to Black cohosh alone in alleviating climacteric mood symptoms.”  Again, the fact that the trial design didn’t include a placebo control means that this study can’t really be seen as support for this intervention.

A sixteen-week, “double-blind randomized placebo-controlled study” (n= 301) of a fixed combination of black cohosh and St. John’s wort (Remifemin plus) concluded that this treatment was, “a reliable and safe means to alleviate climacteric complaints with a predominant psychological component.”

Osmers et al. (n=304) found that, “extract of black cohosh root stock is effective in relieving climacteric symptoms, especially in early climacteric women.”  Liske et al. found that, “is associated with improvement in menopause symptoms without evidence of estrogen like effects” in a study without a placebo control group. 

Rotem and Kaplan reported a small a randomized, double-blind, placebo-controlled trial (n=50) who were given either an, “oral Phyto-Female Complex or matched placebo … twice daily for 3 months.”  This product contained, “standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry [Vitex agnus-castus]”.  They concluded, in part, “Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women”.

What are we to make of this?  As I’ve said I usually prefer to see what a reputable review, preferably by the Cochrane Collaboration, makes of the evidence as a whole.  In this case, there is none; however, there is an alternative approach that can be taken.

R Barker Bausell suggests looking for high quality trials, which meet the following four criteria:

1. The trial involves the random assignment of participants to both a CAM therapy and a credible placebo control group.
2. The trial employs at least fifty participants per group. 
3. The trail doesn’t lose 25 percent or more of its participants over the course of the study.
4. The trial was published in a high-quality, prestigious, peer reviewed journal.

Criterion 4 requires some elaboration; Bausell explains: 

“… there is a relatively objective way to choose high-quality research journals, and that is to look at what is called “journal impact,” which is based upon the number of times a given journal’s research articles are cited by other researchers.  High-impact journals are also the most prestigious medical journals, which means that all medical researchers (CAM and conventional) aspire to have the results of their efforts published therein.  Not coincidentally, they are also the types of journals that the investigators’ funding agencies prefer to see their clients publish in.  The runaway leaders among general (non-disease-specific) American medical journals are the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA); hence … it is these two journals that I initially chose as optimal sources of high-quality CAM trials.”

[Snake Oil Science – The Truth About Complementary and Alternative Medicine, p. 194]

He surveyed these high quality sources between January 2000 and February 2007.  After finding 14 negative trials of CAM interventions and no positive ones he included the Annals of Internal Medicine in his search.  This found the study of black cohosh reported by Newton et al. which concluded that, “Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms.” [emphasis mine]

The other positive trials mentioned that fall outside the timeframe of Bausell’s survey all fail at least one of his criteria, usually criterion 4.  On this basis, I don’t find them very persuasive as evidence.

So, having wrestled with the evidence for Black cohosh as a therapy for relieving menopausal symptoms, I can’t escape the conclusion that the best evidence currently indicates that it is no more help than a placebo.  There is certainly not enough evidence to support retailing pills containing this preparation to help women, “Beat the menopause naturally”.

‘Flash fighters’ also seem to contain: Dong Quai (Angelica sinensis), Licorice (Glycyrrhiza glabra) and Vitex Extract (Vitex agnus-castus) (fruit).

What is the evidence, if any, for these ingredients helping with menopausal symptoms?  The paper by Rotem and Kaplan, mentioned earlier, used a treatment that included Dong Quai and it reported positive results.  However, this was a small trial (n=50) and, to be fair, described itself as a, “pilot study”. 

Other studies have come to different conclusions.  Hirata et al. (n=77) concluded, “Used alone, dong quai does not produce estrogen-like responses in endometrial thickness or in vaginal maturation and was no more helpful than placebo in relieving menopausal symptoms.”  [emphasis mine]  Dong quai also figured in the one arm of the HALT study in a “multibotanical” preparation (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron).  This high-quality trial concluded, “… none of the herbal interventions showed significant effects on any outcomes at any time point.” [emphasis mine]

Searching the Cochrane Library using either “Licorice”, “Liquorice” or “Glycyrrhiza glabra” revealed no relevant clinical reviews or trials.  The same was the case for “Vitex agnus-castus”.  Again, I could find no reliable evidence to support the sale of products containing these ‘botanicals’ which claim to help with menopausal symptoms.

Even NCCAM in their “Get the Facts” section on “Menopausal Symptoms and CAM” say this about some of these ‘botanicals’:

Black cohosh (Actaea racemosa, Cimicifuga racemosa)…Studies of its effectiveness in reducing hot flashes have had mixed results. A study funded by NCCAM and the National Institute on Aging found that black cohosh, whether used alone or with other botanicals, failed to relieve hot flashes and night sweats in postmenopausal women or those approaching menopause. Other research suggests that black cohosh does not act like estrogen, as once was thought.

Dong quai (Angelica sinensis). Only one randomized clinical study of dong quai has been done. The researchers did not find it to be useful in reducing hot flashes.

Ginseng (Panax ginseng or Panax quinquefolius)… ginseng may help with some menopausal symptoms, such as mood symptoms and sleep disturbances, and with one’s overall sense of well-being. However, it has not been found helpful for hot flashes.

Red clover (Trifolium pratense)…five controlled studies found no consistent or conclusive evidence that red clover leaf extract reduces hot flashes.

Soy. The scientific literature includes both positive and negative results on soy extracts for hot flashes.

As NCCAM point out, there may also be health risks to weigh against the dubious efficacy of these plant extracts, such as liver problems (black cohosh); increasing the effect of warfarin (dong quai); damage to hormone-sensitive tissue in the breast and uterus (red clover) and thickening of the lining of the uterus (long-term use of soy extracts).

So, all in all: a deeply cynical and unsupportable marketing campaign by Holland and Barrett.  I’m in the process of seeing what the ASA makes of this.  I do hope that they are able temper Holland and Barrett’s dubious promotional strategy somewhat.

 
[BPSDB]

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