Menopause is a natural transitional part of life that typically affects women between the ages of 45 and 55. It is triggered by a decline in the production of oestrogen from the ovaries, eventually leading to the cessation of menstruation. Although it is a natural part of ageing, the menopause can elicit many symptoms that range from uncomfortable or irritating, to completely debilitating. Oestrogen has multiple roles within the body and this reduction can lead to not only symptoms strongly associated with menopause, such as hot flushes and night sweats, but also can be a trigger for chronic or more serious conditions. Here we look at the functions of oestrogen and how we can use plant-based nutrients with a similar structure to oestrogen to help support women during menopause.

Function of oestrogen:

Puberty and sexual development – growth promoting hormone stimulating breast development, increased weight and height, pubic and axillary hair and beginning of menstrual cycle and ovulation during puberty. It also supports lubrication and integrity of vagina.

Menstrual/ Reproductive Cycle – responsible for thickening of endometrial lining and supporting ovulation as well as maintaining pregnancy.

Bone density – triggers bone growth and development, especially during puberty but also helps to maintain bone density into adulthood by stimulating osteoblast (bone building cells) activity.

Cardiovascular Health –shown to support blood vessel health and flexibility, support blood lipid balance and modulates inflammation. Additionally, oestrogen increases the production of nitric oxide which aids blood vessel relaxation, and therefore is a suggested therapy for acute cardiovascular events in women.

Cognitive function – oestrogen plays many roles in supporting cognitive health, including stimulating serotonin production and supporting synaptic plasticity and memory.²

From the above functions you can see that oestrogen is supporting wellness form many angles and therefore menopausal women can experience adverse effects during, and after, this time. Menopause can increase the risk of cardiovascular disease, osteoporosis, depression and cognitive decline due to the lack of oestrogen¹. Therefore, these systems need to be supported.

Hot flushes and night sweats

The most common, or commonly described, symptoms of menopause are hot flushes and night sweats, these can be incredibly uncomfortable and disruptive to everyday life, work and especially sleep. They are associated with dysregulation of the hypothalamic regulatory system within the brain. Some women will realise a warm sensation before the beginning of a hot flash and will experience an increase in adrenaline associated with increased heart rate and anxiety. Then there is an overreaction leading to sweating, increased pulse and even chest tightness and then coldness. These symptoms are similar to those associated with an increase in adrenaline. The dysregulation of oestrogen levels (during menopause and perimenopause oestrogen levels can significantly fluctuate) triggers the stress response leading to increased adrenaline activation and interferes with the hypothalamic control of temperature¹. In addition, thyroid hormone appears to play a role. Hormonal fluctuations are not just oestrogen driven; however, oestrogen fluctuations are at the centre of these adverse symptoms. Therefore, it is important to help balance oestrogen levels and ameliorate the symptoms of the drop in oestrogen.

Isoflavones³

Isoflavones are phytochemicals which are abundant in soybeans. Active isoflavones found in soy include daidzein, glycitein and genistein, they are considered to be phytoestrogens, thereby elicit a mild oestrogenic effect. Phytoestrogens can weakly occupy oestrogen receptors within the body and stimulate a gentle oestrogenic response.

There are two types of oestrogen receptors: ERα, the predominant form in the breast and uterus, and ERβ, the predominant form in the cardiovascular system, urogenital tract, and bone. Isoflavones bind weakly to Erα but the affinity of isoflavones to ERβ is higher. The estimated estrogenic effects of different isoflavones using human cell cultures in vitro have shown that the relative potencies are genistein 0.084%, and daidzein 0.013%, respectively to that of oestradiol (active form of oestrogen). However, isoflavones can circulate at 10,000 times the concentration of oestradiol and achieve greater binding potential through abundance.

Phytoestrogen-rich soybeans, which are common in Asian diets, are related to a lower incidence of menopausal symptoms, osteoporosis, cardiovascular diseases and hormone-dependent cancers. Hence phytoestrogens have gained wide attention for being able to help attenuate strong hormonal fluctuations that are occurring in menopausal women and also provide a protective influence against longer-term more serious conditions.

Research

Hot flushes³ - studies have shown that the use of isoflavones has improved the incidence of hot flushes in menopausal women. Epidemiological studies have suggested that there is a link between countries that consume soy and decreased hot flushes. Soy intake is estimated to be four to nine times greater in Asian countries such as Japan, Korea, China, Taiwan, and Indonesia, than in Western countries such as the United States, and women in Asian countries report a much lower incidence of hot flushes (10–25%) compared to women in Western countries (60–90%).³

• Cancellieri et al. found that using a herbal supplement containing 72mg of isoflavones from soybeans and red clover for 6 months significantly reduced hot flushes.
• A prospective study of 51 healthy postmenopausal women also found a 57% reduction in the frequency and severity of hot flushes taking 60mg of isoflavones daily for 12 weeks.
• Splitting the dose of soy supplement to twice-daily decreased the severity of hot flushes more than giving the total amount in one dose, suggesting consistent circulating levels of phytoestrogens to be more effective - doses used were 40mg and 60mg.

Cardiovascular – isoflavones from soy have also been shown to improve cardiovascular outcomes, independently of other soy derivatives that may be supportive. The lack of oestrogen leads to a rise in low-density lipoprotein (LDL) cholesterol, endothelial dysfunction, and reduced carotid arterial pulsatility. Isoflavones may be able to reduce cardiovascular risk by acting as oestrogen substitutes. Isoflavones have antioxidative effects and anti-inflammatory actions, as well as induce nitric oxide production to maintain a healthy endothelium and prevent endothelial cell dysfunction. These effects may limit the development of atherosclerosis and CVD and restore healthy endothelial function in altered endothelia⁴.

• Supplementation with soy protein with isoflavones for 6 months significantly improved CVR (cardiovascular risk) markers and calculated CVR at 6 months during early menopause compared to soy protein without isoflavones⁵.

Bone density – as mentioned previously oestrogen plays an essential role in maintaining bone density, therefore a reduction is oestrogen production leads to a gradual loss of bone density, with potential to develop into osteoporosis. Isoflavones have shown a potential for supporting bone density and protecting against osteoporosis³.

• A meta-analysis showed significant attenuation of spinal bone loss after 6 months of over 90mg/day of isoflavone supplement
• Another study found 120mg of isoflavones per day did not slow bone loss at regional bone sites, there was slowing of BMD loss
• A systematic review and meta-analysis published in 2017 reiterated that isoflavones attenuated BMD loss, but more so at the lumbar spine compared to the femoral neck, and isoflavones in aglycone form were more efficacious

Cognitive function – there are limited studies that have unequivocally identified improvements to mood or cognitive function with soy, although many suggest there may be a link. In particular hot flushes have been shown to contribute to depressive symptoms and also activate the HPA axis¹, which can contribute to anxiety and depression. Therefore, ameliorating the effects of hot flushes and hypothalamic signalling may indirectly support other associated cognitive symptoms. Research for the potential of soy isoflavones supporting cognition have shown:

• Of 20 intervention studies identified, roughly half found statistically significant reductions in depressive symptoms in response to isoflavones although several had design weaknesses. Of those studies reporting a lack of antidepressant effects of isoflavones, design limitations likely contributed to the lack of efficacy. In all but two trials, assessment of depression was, however, a secondary outcome. It is notable that both trials in which depression was a primary outcome found isoflavones significantly improved symptoms.^6-7
• One study looking at the effect of phytoestrogens from soy on cognitive function found that phytoestrogen treatment interventions demonstrated time-limited positive effects on cognition. These findings are consistent with oestrogen treatment studies, where initial positive short-term cognitive effects may occur, which reverse with long-term continuous use in elderly women. It was suggested that further large-scale studies were necessary.⁸

Menopause Support (formerly Phytoflavone):

Menopause Support is a Cytoplan product providing 500mg of soy germ per capsule, each containing 50mg isoflavones (daidzein, glycitein and genistein). This provides the whole soy germ which possesses additional benefits of compounds including phytosterols, saponins, phenolic compounds, lecithin, oligosaccharides and vitamin E. These additional compounds elicit their own benefits to health including cognitive and cardiovascular function.

Adrenal Glands

As the production of oestrogen from the ovaries declines, the adrenal glands will take over and produce small amounts of oestrogen which can help to alleviate some of the symptoms associated with menopause. Therefore, once menopause begins the adrenals need to work a bit harder.

The adrenal glands are also responsible for the production of stress hormones, cortisol and adrenaline – if stress is a significant factor, then the adrenals will focus on producing stress hormones at the expense of oestrogen and progesterone. Stress management techniques are important as well as providing nutrients which support adrenal function. This also helps to ameliorate the effects of hypothalamic dysregulation⁹.

Nutrients to support adrenal function include vitamin B5 (pantothenic acid), vitamin B6 (P5P), vitamin C and magnesium. Adaptogenic herbs are also used to support adrenal function, particularly during menopause, these include ashwagandha, ginseng, Bacopa monnieri, Rhodiola and liquorice.

As oestrogen is an important hormone for maintaining bone density, osteoporosis can be a concern post menopause. Therefore, nutrients which are important for bone density may be additionally required including vitamin D3, vitamin K2, magnesium and calcium.

Key Takeaways:

• Menopause is a natural transitional part of life that typically affects women between the ages of 45 and 55. It is triggered by a decline in the production of oestrogen from the ovaries, eventually leading to the cessation of menstruation
• Symptoms strongly associated with menopause such as hot flushes and night sweats can be a trigger for chronic or more serious conditions.
• Isoflavones are phytochemicals which are abundant in soybeans. Active isoflavones found in soy include daidzein, glycitein and genistein, they are considered to be phytoestrogens, thereby elicit a mild oestrogenic effect. Phytoestrogens can weakly occupy oestrogen receptors within the body and stimulate a gentle oestrogenic response.
• Supplementation with isoflavones has been shown to ameliorate symptoms of menopause including hot flushes.
• Isoflavones have demonstrated protective effects for cardiovascular, cognitive and bone health.
• Supporting adrenal funciton is also important during menopause as the adrenal glands take over production of oestrogen for the ovaries. Therefore, adrenal supporting products such as vitamin B5 (pantothenic acid), vitamin B6 (P5P), vitamin C and magnesium may be useful. Adaptogenic herbs are also used to support adrenal function, particularly during menopause, these include ashwagandha, ginseng, Bacopa monnieri, Rhodiola and liquorice.

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If you have questions regarding the topics that have been raised, or any other health matters, please do contact our team of Nutritional Therapists. nutrition@cytoplan.co.uk 01684 310099

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1. Textbook of Functional Medicine (2008) Elsevier
2. Lu Y, Sareddy GR, Wang J, Wang R, Li Y, Dong Y, Zhang Q, Liu J, O'Connor JC, Xu J, Vadlamudi RK, Brann DW. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory. J Neurosci. 2019 Apr 10;39(15):2792-2809. doi: 10.1523/JNEUROSCI.1970-18.2019. Epub 2019 Feb 6. PMID: 30728170; PMCID: PMC6462452.
3. Chen LR, Chen KH. Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview. Int J Mol Sci. 2021;22(6):3212. Published 2021 Mar 22.
4. Yamagata K. Soy Isoflavones Inhibit Endothelial Cell Dysfunction and Prevent Cardiovascular Disease. J Cardiovasc Pharmacol. 2019 Sep;74(3):201-209. doi: 10.1097/FJC.0000000000000708. PMID: 31356541.
5. Sathyapalan T, Aye M, Rigby AS, Thatcher NJ, Dargham SR, Kilpatrick ES, Atkin SL. Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause. Nutr Metab Cardiovasc Dis. 2018 Jul;28(7):691-697. doi: 10.1016/j.numecd.2018.03.007. Epub 2018 Apr 10. PMID: 29739677.
6. Amin Z, Canli T, Epperson CN. Effect of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Rev. 2005 Mar;4(1):43-58. doi:
7. Messina M, Gleason C. Evaluation of the potential antidepressant effects of soybean isoflavones. Menopause. 2016 Dec;23(12):1348-1360. doi: 10.1097/GME.0000000000000709. PMID: 27552470; PMCID: PMC5181104.
8. Soni M, Rahardjo TB, Soekardi R, Sulistyowati Y, Lestariningsih, Yesufu-Udechuku A, Irsan A, Hogervorst E. Phytoestrogens and cognitive function: a review. Maturitas. 2014 Mar;77(3):209-20. doi: 10.1016/j.maturitas.2013.12.010. Epub 2014 Jan 8. PMID: 24486046.
9. Finch CE. The menopause and aging, a comparative perspective. The Journal of steroid biochemistry and molecular biology. 2014;0:132-141.