Menerba, also known as Menopause Formula 101 (MF-101), is a

botanical drug Botany, also called , plant biology or phytology, is the science of plant life and a branch of biology. A botanist, plant scientist or phytologist is a scientist who specialises in this field. The term "botany" comes from the Ancient Greek wo ...

candidate that acts as a

selective estrogen receptor modulator Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...

(SERM) which is being studied for its potential to relieve

hot flashes Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

associated with

menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

. Menerba, an

estrogen receptor beta Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...

(ERβ)

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

(ERBA), is part of a new class of receptor subtype-selective estrogens, which is selective in transcriptional regulation to one of the two known

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...

(ER) subtypes. Menerba consists of 22 herbs that have been used historically in

traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action ...

. Menerba binds to both

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

and ERβ and with equal

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

, but does not activate ERα and instead activates only ERβ-mediated

gene transcription Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...

Mode of action

Menerba has been reported to alleviate menopausal symptoms such as

, while having no stimulative effects on

endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

tissue. In mouse xenograft models, Menerba produced a different conformation in

estrogen receptor alpha Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

(ERα) from ERβ when compared with the conformations produced by

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

. The specific conformational change induced by Menerba allows ERβ to bind to an estrogen response element and recruit coregulatory proteins that are required for

gene activation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wi ...

. It has been shown that the increased risk of breast and uterine cancers is associated with ERα activation and that ERβ blocks the growth promoting effects on

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

cells. Menerba does not activate the ERα-regulated proliferative genes, c-myc and cyclin D1, or stimulate MCF-7 breast cancer cell proliferation or tumor formation, demonstrating that it may be a viable alternative for

hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

in comparison to

estrogens Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

that non-selectively activate both ER subtypes. In 2007, Menerba completed a multi-center Phase 2, double-blind, placebo-controlled randomized

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

evaluating its potential for the treatment of hot flashes in 217 healthy post-menopausal women in the U.S. The

principal investigator In many countries, the term principal investigator (PI) refers to the holder of an independent grant and the lead researcher for the grant project, usually in the sciences, such as a laboratory study or a clinical trial. The phrase is also often us ...

of the trial was Dr. Deborah Grady from the

University of California, San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It cond ...

. Menerba showed a statistically significant reduction in the number of hot flashes after 12 weeks of treatment and had a

statistically significant In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the p ...

reduction in nighttime awakenings from

(-67%, p=0.05). There was no difference in

uterine bleeding Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproduct ...

between treatment groups and

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

, and no uterine abnormalities were observed during the study. The only side effect observed was mild loose stools (12% in treatment group vs. 3% in the

placebo group Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dieta ...

). Further studies have shown that most active estrogenic compound in Menerba is

liquiritigenin Liquiritigenin is a flavanone that was isolated from ''Glycyrrhiza uralensis'', and is found in a variety of plants, including ''Glycyrrhiza glabra'' (licorice). It is an estrogenic compound which acts as a selective agonist of the ERβ subtype ...

, derived from the root of '' Glycyrrhizae uralensis'' Fisch, one of the 22

botanically derived Botany, also called , plant biology or phytology, is the science of plant life and a branch of biology. A botanist, plant scientist or phytologist is a scientist who specialises in this field. The term "botany" comes from the Ancient Greek wo ...

ingredients found in Menerba. In a mouse xenograft model, liquiritigenin activated multiple ER regulatory elements and native target genes with ERβ but not ERα. The ERβ-selectivity of liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. Liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. The results demonstrate that some plants contain highly selective estrogens for ERβ and are as selective as synthetic compounds, but regulate different genes. (PLOs 1 – July 17) and suggests that plant-derived ERb-selective compounds could lead to safer, more attractive alternative therapies for menopausal symptoms. In a further study, Menerba was shown to regulate

calcium influx Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

, which is related to

temperature regulation Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

. Menerba underwent Phase 1 safety trials evaluating its

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

at 10 g/day and 15 g/day doses. No significant toxicities have been observed in any of the animal studies with doses ranging from 2000 mg/kg/day in dogs to 16,000 mg/kg/day in rodents. Due to acceptable toxicity results on the Phase 1 trial, the FDA approved Menerba to initiate a Phase 3 trial with 1200 women reporting seven or more menopausal hot flashes per day.

References

External links

Official Menerba (MF101) website

Official Menerba manufacturer website
{{Estrogen receptor modulators Botanical drugs Herbalism Phytoestrogens Selective ERβ agonists

Mode of action

See also

References

External links