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A Non-Hormone Approach to Menopause Management

October 2018

By Stephanie Clark

Menopausal women can obtain symptomatic relief with proper use of estrogen, progesterone, and other hormones.

Life Extension® has long advocated for bio-identical hormones as opposed to horse urine-derived estrogens and synthetic progestogens.

Some women, however, choose not to replace hormones and endure years of misery.

A non-hormonal approach has been demonstrated with an extract made from Siberian rhubarb. It’s been used successfully in Germany since 1993.

This plant extract has been shown to alleviate 11 menopause symptoms by as much as 83% in human studies.1

Siberian rhubarb extract offers a natural approach for women seeking menopausal relief with a non-hormonal option.

Understanding Menopause

Understanding Menopause  

Menopause is a change of life that no woman can avoid.

It’s characterized by symptoms that may include hot flashes, night sweats, mood changes, sleep disturbances, vaginal dryness, and more.2,3

The Menopause Rating Scale identifies 11 separate symptoms suffered by women in various stages of menopause.4,5 Most of these symptoms are brought on by a decline in a primary female hormone, estrogen.

Estrogen is known for its “feminizing” properties on the breast, uterus, and ovaries. It also affects tissues throughout the body, including bone, brain, heart, and vascular tissues, skin, and even lung and fat tissues.6

The sharp and often sudden drop in estrogen drives most menopausal symptoms.

Many women relieve menopausal symptoms with hormone therapies, but not all women are comfortable with hormone drugs.

What You Need to Know
Menopause Relief

Menopause Relief

  • All women will undergo menopause. The options that can help alleviate the full spectrum of menopausal symptoms are limited.
  • An extract of Siberian rhubarb has been in use for more than two decades for menopausal symptoms in Germany.
  • Multiple human studies have shown that Siberian rhubarb extract significantly reduces all 11 of the recognized menopausal symptoms.
  • In addition to experiencing fewer hot flashes, women taking Siberian rhubarb extract can expect broad spectrum improvements in menopause symptoms, including better mood and better sleep.

The Issue with Standard Treatments

The Issue with Standard Treatments  

Estrogen binds to specific cell receptors, depending on their locations.

Two important estrogen receptors are found throughout the body, but tend to be concentrated in different tissues.

  • Estrogen receptor-alpha (ER-alpha) is primarily found in reproductive (breast, ovary uterine) tissues. When activated, it produces strong effects on female sex organs.6
  • Estrogen receptor-beta (ER-beta) is found in peripheral tissues, where it produces non-sexual effects that sustain tissue flexibility and function.6

Replacing the missing estrogen with nonselective hormone drugs activates the ER-alpha and ER-beta receptors. This can be a double-edged sword, however.

Activating ER-beta promotes beneficial estrogenic effects on skin, brain, bone, cardiovascular, and other tissues.

The problem is that estrogen drugs simultaneously activate ER-alpha that can produce undesirable growth in reproductive tissues, including initiating and promoting cancer.6

Inducing activity of the ER-alpha receptor is the prime suspect in the ill effects of conventional hormone therapy.

A better approach is to selectively activate the ER-beta receptor, while having only a minimal effect on the ER-alpha receptor. That way a woman can promote the beneficial estrogen effects on tissues and organs throughout the body, while avoiding the potential cancer-promoting effects of estrogen on reproductive tissues.6

Fortunately, scientists have found a natural compound that can safely do exactly that, i.e., selectively activate primarily the ER-beta receptor.

An Alternative Way to Treat Menopause Symptoms

An extract from the roots of the Siberian rhubarb plant has been used in Germany since 1993 for menopause symptoms.7

This standardized extract has the highest selectivity for ER-beta over ER-alpha compared to natural estrogen or any other known natural compounds.8,9

The root of Siberian rhubarb is rich in hydroxystilbene compounds including rhaponticin and desoxyrhaponticin.3,7,8

These rhubarb compounds bind to the beneficial ER-beta receptors—the receptors more predominant in skin, brain, bone, heart, and other body areas that suffer during the menopausal estrogen decline.

This Siberian rhubarb extract binds only weakly to ER-alpha receptors.

Laboratory studies show that Siberian rhubarb extract exerts an ER-beta activation 13.5-fold greater than its undesirable ER-alpha effects.8,9

Comparing Siberian Rhubarb Extract to Placebo

Changes in Depressed Mood Symptoms From Baseline13

  Siberian Rhubarb Extract Placebo Siberian Rhubarb

Patients experiencing remission of mood and anxiety symptoms

30.2%

1.8%

Patients experiencing improvement of symptoms

60.4%

23.6%

Patients experiencing no change in symptoms

9.4%

69.1%

Targeted Action

Hot flashes are one of the most well-known symptoms of menopause. They occur in part with fluctuations in estrogen levels.10

Rats that have had their ovaries removed are often used as models of human menopause. These animals go through similar temperature elevations as humans, providing a direct way to measure the impact of an intervention.

Research shows that Siberian rhubarb extract has similar effects on temperature control as estradiol, the main form of natural estrogen. The difference is in its impact on ER-alpha and ER-beta.

Compared to estradiol, Siberian rhubarb extract had much greater selective ER-beta impact on genes in the animals’ hypothalamus, where temperature regulation and other processes are governed.9,11 It had very little impact on ER-alpha receptors, confirming previous lab work.

The true test came in using the plant extract on real women experiencing real menopause symptoms. Siberian rhubarb extract passed that test with flying colors.

Comprehensive Menopause Management

Clinical studies, together examining more than 400 peri- and postmenopausal women, have now evaluated the effects of a 4 mg daily dose of Siberian rhubarb extract.1,3,7,12,13

These studies all used the official Menopause Rating Scale or the newer MRS-II, both of which evaluate a total of 11 menopause symptoms.

Overall, the studies showed that Siberian rhubarb extract consistently reduced the total Menopause Rating Scale symptom severity by up to 83%.

Some women experienced relief as early as four weeks after starting the supplement—and the results lasted up to two years with continuous use of the extract.1,3,7,12,13

What’s more, in addition to reducing the number of hot flashes, Siberian rhubarb extract also led to a significant reduction in mood symptoms such as anxiety and depression—an area where standard conventional treatments often fall short.1,12,13

Let’s briefly examine each study.

Improves All Measured Menopause Symptoms

The first study was a randomized, double-blind, placebo-controlled trial that included 109 perimenopausal women with multiple symptoms. Results for this initial study were reported in two separate publications.3,13

The women received 4 mg/day of Siberian rhubarb extract or a placebo for 12 weeks.3,13 Then they were evaluated using the MRS II and the Hamilton Anxiety Score (reported in a separate publication).

By the end of the study period, total symptom severity scores fell in the Siberian rhubarb extract group by 54%, and there were significant improvements in all 11 symptom categories.3 Placebo recipients had no significant changes, and they continued to experience severe menopausal symptoms.

A few years later, scientists conducting a similar study achieved virtually identical results.12 For this study, 112 symptomatic perimenopausal women took 4 mg/day of Siberian rhubarb extract or a placebo for 12 weeks.

Once again, the results showed:12

  • Overall MRS scores dropped by 54% in the supplemented group.
  • Significant improvements in all 11 of the MRS symptom categories, including an 83% reduction in the median number of daily hot flashes.
  • No significant changes in placebo recipients.

A separate review of 24 placebo-controlled trials found that using conventional hormone therapy reduced the frequency of hot flashes by about 75%.14 This shows that Siberian rhubarb extract achieves similar results compared to conventional hormone replacement therapy for hot flash reductions.

Siberian rhubarb extract is also effective for reducing the other MRS symptoms. Importantly, as the next section explains, this includes the all too often overlooked mood problems associated with menopause.

Life Extension®’s Position on Bioidentical Hormone Replacement Therapy
Bioidentical Hormone Replacement Therapy

Siberian rhubarb extract is a unique, non-hormonal approach to controlling menopausal symptoms, and provides an alternative to hormone replacement therapy.

Hormone replacement therapy in general aims to restore the desirable functions of estrogen in women whose levels are falling as a consequence of menopause. Conventional hormone drugs are often combinations of oral conjugated estrogens derived from pregnant horse urine and synthetic progestins (progestogens). Synthetic progestins are associated with safety risks including raised risks of breast cancer, heart disease, stroke, and blood clot.18

Bioidentical hormone replacement therapy uses hormones identical to those produced in the human body. Because it may be associated with fewer side effects than conventional therapy, bioidentical hormone replacement has become the choice of many women.18

Women using bioidentical hormone replacement therapy should continue to use the treatment if it is providing relief.

For those women who prefer to use a non-hormonal approach, Siberian rhubarb extract is an appealing alternative that provides relief for all 11 symptoms on the Menopause Rating Scale.

For more information on Life Extension’s position on bioidentical hormone replacement therapy, please see the Life Extension Female Hormone Restoration Protocol at www.LifeExtension.com/female.

Boosting Mood

Conventional hormone drugs mostly address hot flashes and night sweats, but often fall short on improving mood symptoms such as anxiety and depression. There is even some evidence that conventional treatments can aggravate these symptoms.15,16

Siberian rhubarb extract is able to reduce the number and severity of hot flashes to a similar extent as conventional hormone replacement therapy, while also improving mood-related symptoms that are not addressed, and are sometimes exacerbated by conventional treatments.3,12,14

Specifically, one study showed that 60% of those taking Siberian rhubarb extract experienced an improvement in depressed mood symptoms, while the placebo group’s symptoms deteriorated during that time.13

Of special note, in one of the papers that arose out of this study, Siberian rhubarb extract produced a 66% reduction in total scores on the Hamilton Anxiety Scale.13 The table on the previous page describes the changes from baseline in the depressed mood symptoms category of the scale.

Long-Term Impact

In order to evaluate the long-term efficacy of Siberian rhubarb extract, researchers tested it in an open-label follow-up study over 108 weeks (just over two years).1

Women who had been taking the extract in a previous double-blind study continued their supplementation, while women who had received placebo began supplementing with the active extract at the end of the prior trial.

Women in the former placebo group rapidly caught up with their peers once they started the active supplement, achieving identical results of up to an 83% reduction in total MRS II scores by the end of the study.1 After two years of taking the extract, hot flashes decreased from about 15 a day to an average of just 1.4 a day.1,3

The Menopause Rating Scale
The Menopause Rating Scale

The Menopause Rating Scale, or MRS, was developed in 2004 as a way of standardizing menopausal symptoms. The MRS is a comprehensive tool for the evaluation of a woman’s menopausal symptoms. The MRS contains 11 symptoms, each of which is rated on a severity scale ranging from 0 (indicating that the symptom is not present) to 4 (5 on the revised MRS II) indicating “very severe.”3-5

The 11 symptoms measured on the MRS include:

  • Hot flashes, sweating
  • Heart discomfort
  • Sleep problems
  • Depressive mood
  • Irritability
  • Anxiety
  • Physical and mental exhaustion
  • Sexual problems
  • Bladder problems
  • Joint and muscle discomfort

Siberian rhubarb extract is a non-hormonal approach that safely reduces scores on each of the MRS symptoms, as well as the total score, at a daily dose of just 4 mg.1,3,7,12,13

Mental and Physical Improvements

In the largest study, 252 women took 4 mg/day of the Siberian rhubarb extract for six months.7

This study is important because it included women beginning to enter menopause (peri-menopausal), as well as those who were past the menopausal transition but still had concerning symptoms.

This study reaffirmed the ability of Siberian rhubarb extract to significantly reduce every one of the 11 MRS symptoms. It also showed a 52% reduction in the overall MRS scores.7

These reductions were significant after three months, and were followed by additional symptom relief over the next three months.

Women whose symptoms were most severe reported the largest overall improvements. In the entire group, the most prevalent reductions were in some of the most commonly reported symptoms:

  • Hot flashes/sweating
  • Sleep problems
  • Irritability
  • Depressed mood

The ability to improve mood symptoms is a big part of what sets Siberian rhubarb extract apart from conventional hormone drug therapy16—and will no doubt be welcomed by perimenopausal women who struggle with depression.

Safety Profile

It should be noted that no relevant safety issues arose in any of the studies of Siberian rhubarb extract cited here, which together involved more than 400 women. No changes in breast, vaginal, or endometrial tissues were seen, nor were there changes in laboratory parameters or vital signs.

During the time that these studies were being carried out, 6.7 million doses were sold in Germany each year.1,17

Natural Progesterone Replacement

This article focuses on a novel way that maturing women can obtain desirable estrogenic effects without the potential harms associated with conventional hormone replacement. The importance of natural progesterone, however, should not be overlooked.

Since the early 1990s, Life Extension has recommended topical application of natural progesterone cream for its many benefits. These creams are available from compounding pharmacies with a doctor’s prescription and in lower-potency, over-the-counter forms for dermal application.

Some women also use oral pregnenolone capsules (50-100 mg/day) that can be converted to natural progesterone in the body.

Like the hormone estrogen, progesterone levels decline as women go through menopause. Restoring these sex hormones can improve quality of life and potentially reduce risk of several degenerative conditions.

Summary

Menopause  

Hot flashes are the most troublesome menopausal symptoms for most women, but it is important to remember that they are just one of 11 menopausal symptoms recognized by experts.

While conventional hormone replacement is considered effective for hot flashes, it leaves much to be desired in providing relief from the other kinds of menopausal symptoms.

A non-hormonal extract from the root of the Siberian rhubarb plant has been in widespread use in Germany since 1993.

In human studies, this extract significantly relieved all 11 recognized menopausal symptoms, including both hot flashes and depressed mood.

Women taking bioidentical hormone replacement therapy for hot flashes should continue to use it when effective. For those interested in broad-spectrum, non-hormonal relief of menopausal symptoms, Siberian rhubarb extract will be an attractive option.

Women who are past their menopausal years, but do not feel as young as they did prior to onset of menopause, may consider trying Siberian rhubarb extract to see if it improves their sense of well-being.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Hasper I, Ventskovskiy BM, Rettenberger R, et al. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause. 2009;16(1):117-31.
  2. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072495/. Accessed July 2, 2018.
  3. Heger M, Ventskovskiy BM, Borzenko I, et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause. 2006;13(5): 744-59.
  4. Available at: http://www.menopause-rating-scale.info/evaluation.htm. Accessed July 3, 2018.
  5. Heinemann LA, DoMinh T, Strelow F, et al. The Menopause Rating Scale (MRS) as outcome measure for hormone treatment? A validation study. Health Qual Life Outcomes. 2004;2:67.
  6. Farzaneh S, Zarghi A. Estrogen Receptor Ligands: A Review (2013-2015). Sci Pharm. 2016;84(3):409-27.
  7. Kaszkin-Bettag M, Beck S, Richardson A, et al. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. 2008;14(6):32-8.
  8. Wober J, Moller F, Richter T, et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. J Steroid Biochem Mol Biol. 2007;107(3-5):191-201.
  9. Konda V, Swick A, Troup JD, et al. Efficacy of Rheum rhaponticum ERr 731® extract in alleviating vasomotor menopausal symptoms in an ovariectomized rat model. Paper presented at: NAMS Annual Meeting2014; Washington, D.C.
  10. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol. 2014;142:115-20.
  11. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022790/. Accessed July 3, 2018.
  12. Kaszkin-Bettag M, Ventskovskiy BM, Solskyy S, et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. 2009;15(1):24-34.
  13. Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause. 2007;14(2):270-83.
  14. Maclennan AH, Broadbent JL, Lester S, et al. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004(4):CD002978.
  15. Available at: http://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-treatments/hormone-therapy-benefits-risks. Accessed July 5, 2018.
  16. Toffol E, Heikinheimo O, Partonen T. Hormone therapy and mood in perimenopausal and postmenopausal women: a narrative review. Menopause. 2015;22(5):564-78.
  17. Chang JL, Montalto MB, Heger PW, et al. Rheum rhaponticum Extract (ERr 731): Postmarketing Data on Safety Surveillance and Consumer Complaints. Integr Med (Encinitas). 2016;15(3):34-9.
  18. Available at: http://www.lifeextension.com/Protocols/Female-Reproductive/Female-Hormone-Restoration/Page-01. Accessed 6 June, 2018.
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