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Jonathan Raas

Alternatives to hormones

WHY


Many women suppose that Hormone Replacement Therapy (HRT) is unnatural and seek other, more natural or alternative ways of managing their menopause symptoms.

In a recent survey, 95% of women said they would try other therapies before HRT because they consider them more natural and because they are worried about the health risks of HRT. (1)


For some women, it is not advisable to go on HRT. Women with breast, ovarian or endometrium cancer or women at high risk of obtaining these diseases should not take HRT without consulting an expert on this matter.

Women with a blood clotting disease are limited in what kind of HRT they can use.


Many women will seek alleviation for their (peri-)menopause symptoms, which are highly important in private life and sometimes even more in their professional activities.

The average age of a woman’s menopause is around 50 - 51 years; this means that a significant number of women will be working through their menopausal transition. (2)

Some menopausal women may report having tiredness, reduced concentration, impaired memory, brain fog, feeling low/depressed and lowered confidence at work.

Hot flushes at work make some women wish to leave their jobs.


HERBAL TREATMENTS

Herbal products are considered possible treatment options and draw on centuries of experience. We think of it not as an alternative medicine but as a part of modern, more holistic medicine.

It would go beyond the scope of this article to cover all possible plants and their derivatives. Therefore, I have selected the most commonly used for menopause symptoms, reviewing the clinical data, the safety profiles and whether or not their use is justified.





Black Cohosh (Cimicifuga racemose) is a traditional drug for the symptomatic relief of rheumatic pain. This herb can help with hot flushes, although not as well as HRT. Black cohosh does not help with anxiety or low mood. Black Cohosh can interact with other medicines, and there are unknown risks regarding safety. The efficacy of black cohosh extract in reducing hot flashes may be attributed to the binding and modulation of key central nervous system receptors for thermoregulation, mood, and sleep (e.g., receptors for serotonin, dopamine, γ-aminobutyric acid (GABA), μ-opioids). It also affects the improvement of metabolism in the brain and its overall activity.

In a systematic review of the literature, Castelo-Branco and co-workers found that both neurovegetative and psychological menopausal symptoms were significantly less pronounced when the extract was used than in the group of women who did not receive it. Higher doses have also been found to be more effective, especially when combined with St. John’s wort (Hypericum perforatum).

Few side effects occurred, which were not more severe than in the placebo group, and it didn’t seem to affect the liver.

I recommended its use for the treatment of menopausal symptoms especially for hot flushes.

 

St John’s Wort (Hypericum perforatum) is a traditional anti-depressant. It can inhibit the reuptake of neurotransmitters like serotonin, noradrenaline and dopamine. A 2008 Cochrane review of 29 studies compared the effectiveness of St. John’s wort extracts to conventional antidepressants and a placebo, on mild to moderate depression. They conclude that St. John’s wort appeared to be as effective as medical antidepressants and more effective than a placebo. (3)

Because it can relieve feelings of anxiety and depression, it’s a valuable remedy for mood swings symptoms that can happen during menopause.

There is a problem that it interacts with other drugs, which makes it a drug we have concerns about, including its reliability regarding dose effectiveness and safety profiles.

Women on tamoxifen must not take St John’s Wort as it makes the cancer treatment ineffective.

I recommend St John’s Wort for mood swings, anxiety and mild to moderate depression in menopausal women on no other medication.

 

Chaste Tree (Vitex agnus-castus L.) We believe monks used it to diminish their sex drive, hence the typical name monk’s pepper.

Chaste tree shows effectiveness for premenstrual syndrome and premenstrual dysphoric disorder (changes in mood during the time before menstruation).

The primary mechanism is dopaminergic, followed by a decreased release of prolactin. 

There was a significant reduction in breast tenderness, oedema, inner tension, headache, constipation and depression as reported in a randomized, controlled study vs. pyridoxine (Vitamin B6), involving 175 women (4). Cyclical breast tenderness was the focus of a double-anonymized, randomized, placebo-controlled study on 97 women over three menstrual cycles (5). The intensity of mastalgia (pain in the breast) was recorded once per cycle using a visual analogue scale. The differences were more significant in the verum (with Chaste Tree) than in the placebo group.

A fluoxetine-controlled, double-anonymized, randomized study concluded that chaste tree effectively treats premenstrual dysphoric disorder; however, fluoxetine was more effective on all endpoints (6).

Gerhard et al. (7), who investigated chaste tree effects in 96 women with fertility disorders (secondary amenorrhoea, luteal insufficiency, idiopathic infertility), found that pregnancy or spontaneous menstruation was achieved significantly more often in the verum than in the placebo group.

Based on the reviewed data, I conclude that chaste tree is effective and safe in treating premenstrual syndrome and premenstrual dysphoric disorder.

I also recommend Vitex Agnus Castus in the pre-menopause with cycle anomalies and for women with breast tenderness due to hormonal imbalance.

 

Evening primrose (Oenothera biennis)

The seed oil is used in inflammatory conditions such as atopic dermatitis, eczema and rheumatoid arthritis, and in women’s conditions.

The mechanism of action of the oil is attributed to the effects of omega-6 fatty acids on immune cells and the synthesis of prostaglandins, cytokines and cytokine mediators.

Questionnaire-based clinical studies show contradictory results, benefits seem to be at a level of a placebo effect.

Oenothera oil treatments were not found to be associated with major side effects.

I consider it may be reasonable to give the Evening primrose oil therapy a try, together with suitable nutritional approaches, the use of exercise and mind–body techniques in premenstrual syndrome and menopausal symptoms.

 

Fenugreek (Trigonella foenum-graecum L.)

Part of its activity is due to the alkaloid trigonelline, which is a phytoestrogen, as it activates the oestrogen receptor.

A recent (2020) randomized, double-blind, placebo-controlled study on perimenopausal women taking 500 mg fenugreek extract for 42 days showed a more than 20% reduction in hot flashes, night sweats, insomnia, and more than 30% improvement of depression (8). Increases in serum 17-estradiol, free testosterone and progesterone were observed, and decreases in follicle-stimulating hormone and steroid hormone-binding globulin.

In terms of safety and possible interactions, fenugreek is generally safe, but patients taking antidiabetic drugs should monitor their blood sugar regularly. Fenugreek can cause digestive disorders and allergic reactions. It should not be taken during pregnancy due to uterine stimulatory and abortifacient activities. Moreover, data suggest embryo-lethal effects, testicular toxicity and decreased thyroid hormone levels.

Surely I do not recommend it in woman with hormone related cancer or at high risk for this condition.

I would like to see more studies done as it seems to be effective but on the other hand it might have nasty side effects.

 

Hops (Humulus lupulus L.)

We all know hop is important for the production of beer. Extracts can relief mild symptoms of mental stress and aid sleep. Hops has a strong estrogenic activity, e.g., women, harvesting hops by hand started menstruating two days after the hops harvesting began. A prospective, randomized, double-blind, placebo-controlled trial (12 weeks, 67 post- menopausal women showed a significant decrease in menopausal symptoms (9). A dose-response relationship could not be established as a higher dose was less effective than the lower dose. Other studies did not find any benefit compared to placebo.

I recommend hops to alleviate sleeping problems, especially in stressed women.

Because of its oestrogen activity, it should not be prescribed in woman with hormone related cancer or at high risk of such.

 

Red Clover (Trifolium pratense L.)

Red clover contains isoflavones as formononetin, biochanin A, daidzein and genistein. Isoflavones act as phytoestrogens (plant-oestrogens), as they activate the oestrogen receptor. In Australia, breeding problems were observed in sheep herds fed on clover, bringing to attention the oestrogenic effects. Due to coumarin in red clover, it also acts as an anticoagulant. Therefore, particular attention is needed in women taking medicines that help prevent blood clots.

Ever since, many clinical studies were done to evaluate its impact on menopausal symptoms. They showed a positive effect of red clover isoflavones on the relief of hot flashes and menopausal inconveniences experienced in peri- and postmenopausal women.

As a supplement it is likely safe. I recommend its use in the treatment of menopause symptoms, in women not on anticoagulants.

Because of its oestrogen activity, it should not be prescribed in woman with hormone related cancer or at high risk of such.

 

Wild soybean (Glycine soja)

Soy isoflavones are of particular interest in the pharmaceutical industry. They mimic oestrogen and are thus classified as phytoestrogens. They have antioxidant properties. Currently, the available evidence does not support the use of soy and derived products in the relief of menopausal symptoms. This is mostly due to the poor quality of the studies conducted. It appears, however, that genistein content plays a crucial role in the effectiveness of the soy-based supplement. As soy and derived products have a good safety profile (apart from being contraindicated in case of soy allergy or levothyroxine therapy), women suffering from hot flashes and night sweats may still try to alleviate them with soy supplements.


White Kwao Krua (Pueraria mirifica)

In traditional Thai medicine, the roots of Pueraria Mirifica have been taken for centuries to promote youthfulness and rejuvenation in both men and women.

They have a high content of natural phytoestrogens like daidzein, genistein, puerarin, miroestrol and deoxymiroestrol. Miroestrol and deoxymiroestrol show a very high oestrogenic activity; they can act through competition with oestrogen for binding to the oestrogen receptor, where they act as activators.

Research has indicated that the use of Kwao Krua can be almost as effective as oestrogen therapy for systemic symptoms in postmenopausal women.

Research has shown that 25–100 mg daily seems safe, with no apparent adverse reactions reported.

In rabbits, the supplement altered the plasma lipid profile by reducing LDL-cholesterol, increasing HDL-cholesterol and improving vascular health, similar to what we see in humans on an oestrogen replacement when initiated at the moment they enter menopause. (10)

Some animal studies suggest supplementing with Pueraria Mirifica may prevent bone loss.

A topical application in the form of a gel containing 1% Kwao Krua significantly improves the health of vaginal tissue, suggesting it may be an effective therapy for vaginal dryness.

More research is needed to evaluate whether we can observe the same results in humans.

Miroestrol and deoxymiroestrol can potentially cause human breast cancer cells to grow, just like what might happen if a woman goes on oestrogen replacement. (11)

That is the reason why it should indeed not be prescribed in women with hormone-related cancer or at high risk of such.

I do approve of its supplementation in menopausal women with an unfavourable lipid profile at higher risk of cardiovascular disease and women with a family history of osteoporosis.


LITERATURE


1. DepressionTalk.net. (n.d.). Herbal Remedies For Depression During Menopause. Retrieved January 4, 2024, from https://www.depressiontalk.net/herbal-remedies-for-depression-during-menopause/


2. East Sussex Wellbeing At Work. (n.d.). Resources Archive. Retrieved January 4, 2024, from https://wellbeingatwork.eastsussex.gov.uk/resources/


3. Cochrane. (n.d.). St. John's wort for treating depression. Retrieved January 4, 2024, from https://www.cochrane.org/CD000448/DEPRESSN_st.-johns-wort-for-treating-depression


4. Lauritzen, C., Reuter, H.D., Repges, R., Böhnert, K.J., & Schmidt, U. (1997). Treatment of premenstrual tension syndrome with Vitex agnus castus: Controlled, double-blind study versus pyridoxine. Phytomedicine, 4, 183–189.


5. Halaska, M., Beles, P., Gorkow, C., & Sieder, C. (1999). Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: Results of a placebo-controlled double-blind study. Breast, 8, 175–181.


6. Ciotta, L., Pagano, I., Stracquadanio, M., Di Leo, S., Andò, A., & Formusco, C. (2011). Psychic aspects of the premenstrual dysphoric disorders: New therapeutic strategies: Our experience with Vitex agnus castus. Minerva Ginecol, 63, 237–245.


7. Gerhard, I., Patek, A., Monga, B., Blank, A., & Gorkow, C. (1998). Mastodynon® bei weiblicher Sterilität. Forsch Komplementärmed, 5, 272–278.


8. Khanna, A., John, F., Das, S., Thomas, J., Rao, J., Maliakel, B., & IM, K. (2020). Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study. Journal of Food Biochemistry, 44, e13507. https://doi.org/10.1111/jfbc.13507


9. Heyerick, A., Vervarcke, S., Depypere, H., Bracke, M., & De Keukeleire, D. (2006). A first prospective randomized double-blind placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas, 54, 164–175.


10. Ratanachamnong, P., Phivthong-Ngam, L., & Namchaiw, P. (2020). Daily White kwao krua dietary supplement alleviates LDL oxidative susceptibility, plasma LDL level and improves vasculature in a hypercholesterolemia rabbit model. Journal of Traditional and Complementary Medicine, 10(5), 496-503. https://doi.org/10.1016/j.jtcme.2020.05.001


11. Matsumura, A., Ghosh, A., Pope, G., & Darbre, P. (2005). Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells. The Journal of Steroid Biochemistry and Molecular Biology, 94(5), 431-443. https://doi.org/10.1016/j.jsbmb.2004.12.041


Dr. Paul Raas

04/01/2024

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