Menopausal Hormone Therapy in Older Women: Examining the Current Balance of Evidence

David, Paru S.; Sobel, Talia; Sahni, Sabrina; Mehta, Jaya; Kling, Juliana M.

doi:10.1007/s40266-023-01043-3

Cited by 5 publications

(7 citation statements)

References 82 publications

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“…An assessment of risk to benefit consideration for prescribing HT in menopause is always warranted due to potential increased risks for cardiovascular events, stroke, and breast cancer. 41 Nonhormonal options for menopausal symptoms provide additional options for symptom treatment. The only U.S. Food and Drug Administration–approved nonhormonal therapy option currently includes selective serotonin reuptake inhibitors such as paroxetine, which are metabolized by CYP2C19 and CYP2D6 and may be less effective in population with polymorphisms for these genes.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms

Bonga,

Mishra,

Maiti

et al. 2024

Obstetrics &Amp; Gynecology

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OBJECTIVE: To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. DATA SOURCES: PubMed/MEDLINE, ClinicalTrials.gov, EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. METHODS OF STUDY SELECTION: Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. TABULATION, INTEGRATION, AND RESULTS: The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84–3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was −0.60 (95% CI, −0.92 to −0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35–29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. CONCLUSION: Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023427616.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms

Bonga,

Mishra,

Maiti

et al. 2024

Obstetrics &Amp; Gynecology

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“…Eighty-five percent of peri- and postmenopausal women experience various menopausal symptoms, including hot flushes, night sweats, sleep disturbances, mood imbalances, loss of libido, weight gain, and vaginal dryness, that can last for decades [ 156 , 157 ]. Apart from debilitating symptoms impacting the quality of life, the significant loss of hormones experienced at these stages of life results in substantial increases in morbidity and life-threatening conditions, ranging from osteoporosis to cardiovascular disease [ 158 ].…”

Section: Clinical Application: Endocrine System Supportmentioning

confidence: 99%

Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses

Minich,

Ross,

Frame

et al. 2024

Nutrients

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Maca (Lepidium meyenii, Lepidium peruvianum) is part of the Brassicaceae family and grows at high altitudes in the Peruvian Andes mountain range (3500–5000 m). Historically, it has been used as a nutrient-dense food and for its medicinal properties, primarily in enhancing energy and fertility. Scientific research has validated these traditional uses and other clinical applications by elucidating maca’s mechanisms of action, nutrition, and phytochemical content. However, research over the last twenty years has identified up to seventeen different colors (phenotypes) of maca. The color, hypocotyl size, growing location, cultivation, and post-harvest processing methods can have a significant effect on the nutrition content, phytochemical profile, and clinical application. Yet, research differentiating the colors of maca and clinical applications remains limited. In this review, research on the nutrition, phytochemicals, and various colors of maca, including black, red, yellow (predominant colors), purple, gray (lesser-known colors), and any combination of colors, including proprietary formulations, will be discussed based on available preclinical and clinical trials. The gaps, deficiencies, and conflicts in the studies will be detailed, along with quality, safety, and efficacy criteria, highlighting the need for future research to specify all these factors of the maca used in publications.

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“…It has become evident that a continual E2-deficient state recognized as post-menopause broadly and adversely impacts neural and behavioral functions especially those associated with the prefrontal cortex, hippocampus, and hypothalamus ( 9 , 19 , 27 , 70 – 72 ). This may lead to or exacerbate a constellation of symptoms such as cognitive frailty, mood and sleep disturbances, vasomotor symptoms (VMS), as well as susceptibility to develop age-related neurodegenerative diseases, among them Alzheimer’s disease—just to mention a few unpleasant consequences of the hypoestrogenic or estrogen-deficient aging female brain ( 39 , 40 , 74 , 77 , 78 ).…”

Section: E2 and The Aging Female Brainmentioning

confidence: 99%

“…VMS are commonly accompanying these periods manifesting hot flushes and/or night sweats with varying severity among women and, also, over time within an individual. It is estimated that around three-fourths of women experience midlife hot flushes now considered the hallmark symptom of menopause ( 39 , 40 , 90 , 91 ). Women with frequent VMS also experience higher rates of depression, anxiety, and sleep disturbances lowering their quality of life.…”

Section: E2 and Vms (Hot Flushes)mentioning

confidence: 99%

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The impact of 17β-estradiol on the estrogen-deficient female brain: from mechanisms to therapy with hot flushes as target symptoms

Prokai-Tatrai,

Prokai

2024

Front. Endocrinol.

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Sex steroids are essential for whole body development and functions. Among these steroids, 17β-estradiol (E2) has been known as the principal “female” hormone. However, E2’s actions are not restricted to reproduction, as it plays a myriad of important roles throughout the body including the brain. In fact, this hormone also has profound effects on the female brain throughout the life span. The brain receives this gonadal hormone from the circulation, and local formation of E2 from testosterone via aromatase has been shown. Therefore, the brain appears to be not only a target but also a producer of this steroid. The beneficial broad actions of the hormone in the brain are the end result of well-orchestrated delayed genomic and rapid non-genomic responses. A drastic and steady decline in circulating E2 in a female occurs naturally over an extended period of time starting with the perimenopausal transition, as ovarian functions are gradually declining until the complete cessation of the menstrual cycle. The waning of endogenous E2 in the blood leads to an estrogen-deficient brain. This adversely impacts neural and behavioral functions and may lead to a constellation of maladies such as vasomotor symptoms with varying severity among women and, also, over time within an individual. Vasomotor symptoms triggered apparently by estrogen deficiency are related to abnormal changes in the hypothalamus particularly involving its preoptic and anterior areas. However, conventional hormone therapies to “re-estrogenize” the brain carry risks due to multiple confounding factors including unwanted hormonal exposure of the periphery. In this review, we focus on hot flushes as the archetypic manifestation of estrogen deprivation in the brain. Beyond our current mechanistic understanding of the symptoms, we highlight the arduous process and various obstacles of developing effective and safe therapies for hot flushes using E2. We discuss our preclinical efforts to constrain E2’s beneficial actions to the brain by the DHED prodrug our laboratory developed to treat maladies associated with the hypoestrogenic brain.

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Menopausal Hormone Therapy in Older Women: Examining the Current Balance of Evidence

Cited by 5 publications

References 82 publications

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms

Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms

Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses

The impact of 17β-estradiol on the estrogen-deficient female brain: from mechanisms to therapy with hot flushes as target symptoms

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