Menopause

Menopause is becoming one of the key issues to address in women-targeted natural solutions, as its symptoms may affect modern women for about 1/3 of their life.

The drop in hormone levels causes significant imbalances in the endocrine system, which can have heavy repercussions on biological functions – well beyond reproductive mechanisms. The physiological changes that accompany this transition to infertility include a series of well-known symptoms, such as hot flashes, night sweats, sleep disorders, irritability, and reduced libido.

Ginseng, the world-renown elixir of youth and undisputed leader of Asian medicinal plants, has earned a solid reputation for the prevention of age-related discomforts; a centuries-old notoriety now backed up by an increasing number of scientific studies.

Interestingly enough, ginsenosides – the bioactive triterpene fraction of ginseng – do not demonstrate significant estrogenic activity despite having a very similar structure to that of steroid hormones. Ginseng's bioactive constituents could nevertheless be of real interest in the management of menopausal discomfort symptoms through alternative routes of action.

Menopausal discomfort symptoms include a variety of neurological issues, among which important mood swings and persistent sleeping issues. Although hormonal changes are at the source of these discomforts, their resulting metabolic cascades – serotonergic, GABAergic or even BDNF levels – could also constitute potential targets for non-estrogenic treatment strategies aiming at improving postmenopausal women well-being.

Some specific rare ginsenosides have an interesting effect in this respect. The Rg5/Rk1 tandem (bioactive forms of Rb1) has been identified as beneficial for sleep enhancement through GABAergic and serotonergic signalling [3]. To a similar extent, Rg3 (another bioactive form of Rb1) has also been reported to impact sleep through GABAergic activity [4]. In addition, it should be noted that Rg3 has been identified as an “anxiolytic ginsenoside” by several studies [5-7].

Finally, ginsenosides Rg5 and Rg3 have also demonstrated significant anxiolytic activity through BDNF activation [8-9]. BDNF is crucial in postmenopausal women as it is initially stimulated by oestradiol and is therefore potentially under-expressed during the menopausal transition. In addition to mood and neuroprotection -related benefits, BDNF can also be of interest for the prevention of neurodegenerative diseases such as Alzheimer's, to which menopausal women are more susceptible.

Menopause is traditionally associated with an increased risk of metabolic imbalance. This can lead to overweight, dyslipidaemia and, to a lesser extent, to an increased risk of cardiovascular issues. These aspects of metabolic imbalance can be addressed through a variety of physiological pathways – including approaches related to gut microbiota regulation.

For metabolic balance, black ginseng – Panax ginseng roots steam-cooked 9 times or more – is considered the most effective [10]. This higher efficacy is due to an increased relative abundance of specific ginsenosides Rg5 and Rk1, bioconverted from common ginsenosides precursors by the cooking process. Indeed, it has been reported that these compounds positively influence both glycaemic control and lipid metabolism [11-14]. In addition, Rg3 has also been identified as an active ginsenoside for metabolic regulation [15-20].

Oestrogens play a key role in bone health, acting both as a potent anti-resorptive agent and stimulator of osteoblastic differentiation, but also as a regulator of intestinal calcium absorption. The drop in oestrogen levels in postmenopausal women induces a calcium deficiency that results in an increase in osteoclasts-mediated bone resorption rates. This phenomenon leads to a loss of up to 5% of bone mass per year during the menopausal transition, with subsequent risks of osteoporotic fractures [21].

Although hormone therapy is the obvious therapeutic pathway to alleviate this problem, there may also be value in promoting optimal bone health in postmenopausal women through a systematic approach, and ginseng may be a promising avenue.

Indeed, several recent studies have demonstrated the effect of bioactive ginsenosides from red ginseng – notably Rg5, Rk1 and Rg3 – on the differentiation, growth, and proliferation of murine pre-osteoblastic cell lines [22-23]. Rg3 shows potential as a promising treatment for osteoporosis by inhibiting osteoclast genesis and subsequently reducing bone resorption [24-25]. Other mechanisms of action of Rg3 on the alleviation of osteoporosis have also been identified, including increased resistance to oxidative stress, regulation of growth factors and facilitation of bone formation [26].

A growing number of scientific papers report the link between the gut microbiota and hormonal regulation (osteogenic-microbiota axis) [27]. This interaction should therefore not be overlooked in the treatment of menopausal symptoms.

Recently, several active compounds of Panax ginseng [28-29], including specific polysaccharides [30-32] and bioactive ginsenosides such as Rh4 & Rk3 [33-35], have been identified as beneficial for the gut microbiota. While it is too early to state that specific ginseng compounds support postmenopausal women through this microbiotic dimension, a growing body of data points in this direction.

In conclusion, ginseng saponins – and their noble bioactive forms – demonstrate a multi-target action on various menopausal symptoms and could thus help women through their peri-menopausal transition with significant symptomatic alleviation.

Ginseng and its active compounds could therefore constitute an effective, natural, and non-hormonal alternative to improve the existing Nutraceutical offer for (pre-) menopausal women's health and well-being; a new applicative potential for ginseng that deserves further investigation to ensure its safe and free of side effects use in a clinical context.

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