LINK -https://www.ahajournals.org/doi/10.1161/circulationaha.106.642280

SUMMARY

Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. 

LINK - https://pubmed.ncbi.nlm.nih.gov/39077777/

SUMMARY -

Yes it is real!!! And not in our head. More than 70% will experience musculoskeletal symptoms and 25% will be disabled by them through the transition from perimenopause to postmenopause. This often-unrecognized collective of musculoskeletal symptoms, largely influenced by estrogen flux, includes arthralgia, loss of muscle mass, loss of bone density and progression of osteoarthritis, among others.

LINK -https://pmc.ncbi.nlm.nih.gov/articles/PMC6821450/

This Position Statement was developed, by consensus between the participating organizations, to inform health care professionals of the known benefits and potential risks of testosterone therapy for women. The aims were to provide clear guidance as to which women might benefit from testosterone therapy, to identify symptoms, signs, and conditions for which evidence does not support the prescribing of testosterone, to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm.

LINK -https://menopause.org/wp-content/uploads/professional/nams-2022-hormone-therapy-position-statement.pdf

Hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.

The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing therapy.

For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss.

LINK -https://menopause.org/wp-content/uploads/professional/2023-nonhormone-therapy-position-statement.pdf

Evidence-based review of the literature.

Recommended: Cognitive-behavioral therapy, clinical hypnosis, selective serotonin reuptake inhibitors/ serotonin-norepinephrine reuptake inhibitors, gabapentin, fezolinetant ; oxybutynin; weight loss, stellate ganglion block

Not recommended: Paced respiration; supplements/herbal remedies; cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, suvorexant, soy foods and soy extracts, soy metabolite equol, cannabinoids, acupuncture, calibration of neural oscillations; chiropractic interventions, clonidine; dietary modification and pregabalin

LINK -https://pubmed.ncbi.nlm.nih.gov/38484309/

Both treatment for symptoms and training of women's health care practitioners in the management of menopause have sharply declined since publication of the Women's Health Initiative initial results in 2002.

Our patients deserve a more nuanced, individualized approach. Conjugated equine estrogens and medroxyprogesterone acetate are no longer the predominant medications or medications of choice available for management of menopausal symptoms.

All hormones are not equivalent any more than all antiseizure medications or all antihypertensives are equivalent; they have different pharmacodynamics, duration of action, and affinity for receptors, among other things, all of which translate to different risks and benefits.

Consideration of treatment with the right formulation, at the right dose and time, and for the right patient will allow us to recommend safe, effective, and appropriate treatment for people with menopausal symptoms.

LINK -https://pubmed.ncbi.nlm.nih.gov/37847875/

Use of menopausal hormone therapy (HT) fell precipitously after 2002, largely as a result of the Women's Health Initiative's report claiming that the combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased breast cancer risk and did not improve quality of life.

More recently, Women's Health Initiative (WHI) publications acknowledge HT as the most effective treatment for managing menopausal vasomotor symptoms and report that CEE alone reduces the risk of breast cancer by 23% while reducing breast cancer death by 40%. Their sole remaining concern is a small increase in breast cancer incidence with CEE and medroxyprogesterone acetate (1 per 1,000 women per year) but with no increased risk of breast cancer mortality.

This article closely examines evidence that calls even this claim of breast cancer risk into serious question, including the WHI's reporting of nonsignificant results as if they were meaningful, a misinterpretation of its own data, and the misleading assertion that the WHI's findings have reduced the incidence of breast cancer in the United States.

A generation of women has been deprived of HT largely as a result of this widely publicized misinterpretation of the data. This article attempts to rectify this misunderstanding, with the goal of helping patients and physicians make informed joint decisions about the use of HT.

LINK - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061559

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. 

LINK - https://www.ahajournals.org/doi/10.1161/CIR.0000000000000912

SUMMARY

Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman’s risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women’s health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. 

LINK - https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/04/postmenopausal-estrogen-therapy-route-of-administration-and-risk-of-venous-thromboembolism

SUMMARY - Recent studies suggest that orally administered estrogen may exert a prothrombotic effect, whereas transdermally administered estrogen has little or no effect in elevating prothrombotic substances and may have beneficial effects on proinflammatory markers. 

LINK - https://pubmed.ncbi.nlm.nih.gov/38653905/

SUMMARY -

Findings from 10 randomized trials included 14,282 participants and 591 incident breast cancers.

Conclusion: The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use significantly reduces breast cancer incidence.

JOURNAL LINK- https://www.nature.com/articles/s44294-025-00061-3

The results of a survey of 4432 U.S. women about clinical help-seeking and the presence and severity of perimenopause symptoms. By assessing the reported frequencies of consultations and symptoms, we found high rates of consultation with doctors about perimenopause and significant symptom burden, even in individuals aged 30–45 years.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

https://pubmed.ncbi.nlm.nih.gov/41025376/

https://pubmed.ncbi.nlm.nih.gov/40519046/

Conclusions: Use of menopausal hormone therapy was associated with significant improvement in mood in peri- and postmenopausal women. Prospective studies and randomised clinical trials are needed to assess the effects of different regimens in different patient populations over longer time periods.

https://www.mdpi.com/2075-4426/16/5/231

Results: Improvement was reported across all eight domains, with energy/fatigue showing the strongest response (84.3% improved). Depression, irritability, anhedonia, and sexual interest each exceeded 65% improvement. Cognitive domains showed a delayed trajectory, with meaningful gains emerging at 4 to 6 months. Quality of life improvement was reported by 89.7%, with significant improvement rising from 5.4% at 1 month to 51.5% at greater than 12 months. Energy/fatigue (64.2%) and mood (49.7%) ranked above sexual desire (41.3%) as self-identified areas of greatest benefit.

Conclusions: Individualized TRT in women was associated with broad symptomatic improvement spanning energy/fatigue, depression, irritability, anhedonia, cognitive function, and sexual interest, with duration-dependent gains