Botanical modulation of menopausal symptoms: mechanisms of action?

Abstract

Menopausal women suffer from a variety of symptoms, including hot flashes and night sweats, which can affect quality of life. Although it has been the treatment of choice for relieving these symptoms, hormone therapy has been associated with increased breast cancer risk leading many women to search for natural, efficacious, and safe alternatives such as botanical supplements. Data from clinical trials suggesting that botanicals have efficacy for menopausal symptom relief have been controversial, and several mechanisms of action have been proposed including estrogenic, progestogenic, and serotonergic pathways. Plant extracts with potential estrogenic activities include soy, red clover, kudzu, hops, licorice, rhubarb, yam, and chasteberry. Botanicals with reported progestogenic activities are red clover, hops, yam, and chasteberry. Serotonergic mechanisms have also been proposed since women taking antidepressants often report a reduction in hot flashes and night sweats. Black cohosh, kudzu, kava, licorice, and dong quai all either have reported 5-hydroxytryptamine receptor 7 ligands or inhibit serotonin reuptake, therefore have potential serotonergic activities. Understanding the mechanisms of action of these natural remedies used for women's health could lead to more efficacious formulations and to the isolation of active components which have the potential of becoming effective medications in the future.

Figure 1

Classical mechanisms of the estrogenic and progestogenic activities.

Figure 2

Mechanism of serotonergic activity. Serotonin is released in the synapses and binds to its receptor (5-HT₇) in the post synaptic cells. Serotonin receptor, coupled with a G-protein, activates adenylate cyclase, resulting in production of cAMP and activation of enzymatic cascades leading to serotonergic effects.

Figure 3

Chemical structures of phytoestrogens found in the estrogenic botanicals.

Figure 3

Chemical structures of phytoestrogens found in the estrogenic botanicals.

Figure 4

A) P450-catalyzed formation of daidzein and genistein from formononetin and biochanin A, respectively. B) Metabolic formation of 8-PN from its precursors in hops. C) Metabolic formation of liquiritigenin from isoliquiritigenin in licorice.

Figure 5

Chemical structures of phytoprogestins found in botanicals.

Figure 6

Chemical structures of serotonergic compounds found in botanicals.

Figure 6

Chemical structures of serotonergic compounds found in botanicals.