MenopauseArticles Wiki

A living synthesis mined nightly by VaultMiner. Domain: Peer-reviewed articles and citations (menopause, HRT, testosterone, APOE4; papers with DOIs)

Last updated: 2026-08-07

Women's Health Initiative (WHI)

• The Women's Health Initiative estrogen-plus-progestin arm enrolled 16,608 women and was stopped early in 2002. (source: rossouw-2002-jama-whi.md)
• In younger women who entered the trial of estrogen-only therapy with oophorectomy, the intervention was associated with a significant 32% reduction in all-cause mortality over long-term follow-up. (source: Manson2020.md)
• The WHI trials closed early in 2002 in part because of increased cardiovascular disease events seen in women on treatment. (source: Mehta2019.md)

APOE4 and Alzheimer's Disease

• The APOE4 epsilon4 allele is a major risk factor for Alzheimer's disease across all ethnic groups, ages 40-90, and both sexes. (source: farrer-1997-jama-apoe4.md)

Sarcopenia and Menopause

• Sarcopenia in menopausal women is reviewed in Shrikhande et al. 2025, focusing on prevalence, risk factors, and management strategies. (source: shrikhande-2025-jmh-sarcopenia.md)
• Among postmenopausal women, higher SHBG concentrations at baseline were associated with lower lean body mass and higher odds of sarcopenia, while higher free estradiol and free testosterone concentrations were associated with lower odds of sarcopenia. (source: osmancevic-2026-endogenous-sex-hormones-sex-hormone-binding-globulin-and-muscle.md)

Testosterone Measurement and Effects

• The Beckman immunoassay correlates poorly (R² approx 0.16) with the CDC/LC-MS reference method at female-range testosterone concentrations. (source: cao-2017-cca-testosterone-immunoassay.md)
• SHBG elevation from oral contraceptive use can persist after discontinuation, as shown in Panzer et al. 2006. (source: panzer-2006-jsm-shbg-ocp.md)
• Testosterone therapy was associated with significant improvement in menopause symptoms in women with a history of breast cancer. (source: Glynne2026.md)
• Subcutaneous injection of testosterone is an effective and preferred alternative to intramuscular injection. (source: Spratt2017.md)
• Testosterone alters muscle morphology in young women, resulting in type II fiber hypertrophy and improved capillarization. (source: Horwath2020.md)
• Testosterone levels are approximately 50% lower at age 40 compared to the early-20s peak in premenopausal women. (source: Zumoff1995.md)
• Androgen levels show continuous age-related decline in women, with no step-change at menopause. (source: Davison2005.md)
• Transdermal testosterone (2 mg/day) significantly increased total testosterone and Free Androgen Index, improving sexual desire and satisfaction in postmenopausal women with hypoactive sexual desire disorder. (source: CeccattoAndrade2026.md)
• Testosterone therapy is effective for improving key aspects of sexual function in both premenopausal and postmenopausal women, with the strongest evidence supporting its use in postmenopausal women. (source: furlan-2026-testosterone-therapy-for-female-sexual-dysfunction-a-systematic.md)
• 17α-hydroxylase deficiency (17-OHD) should be considered in patients presenting with disorders of sex development or primary hypertension, as it can cause markedly elevated ACTH levels and significantly decreased cortisol levels. (source: zhang-2026-be-alert-to-hypertension-caused-by-17-hydroxylase-deficiency.md)
• Sustained-release ashwagandha root extract (AshwaSR 300 mg/day) significantly increased testosterone levels in men but showed non-significant increases in women while improving muscle strength and cardiorespiratory endurance. (source: thanawala-2026-efficacy-and-safety-of-sustained-release-ashwagandha-root.md)
• Dietary fennel extract increased serum testosterone levels in layer breeders, while garlic and fennel extracts increased female offspring sex ratio. (source: bardel-2026-effect-of-sex-hormones-garlic-and-fennel-extracts.md)
• Dehydroepiandrosterone (DHEA) treatment in pulmonary hypertension significantly increased serum testosterone levels alongside DHEA-S levels. (source: sanders-2026-effects-of-dehydroepiandrosterone-in-pulmonary-hypertension-ediphy.md)

Vaginal Estrogen

• Postmenopausal women (>55) on estrogen (vaginal) had lower rates of hospitalization, sepsis (10.6% vs 19.4%), and death (0.42% vs 1.54%) in recurrent UTI. (source: vaginal-estrogen-rUTI-epic-cosmos-2025-AUA-IP15-36.md)
• Safety of vaginal estrogen in breast cancer survivors is supported by current evidence on systemic absorption and oncologic outcomes. (source: Mainar2026.md)

Menopausal Hormone Therapy (MHT)

• The 2022 hormone therapy position statement of The North American Menopause Society updates recommendations for HRT use. (source: NAMS2022.md)
• The FDA announced removal of the boxed warning on HRT products in 2025. (source: Sriprasert2026.md)
• The timing hypothesis suggests that the cardiovascular effects of HT depend on the timing of initiation of HT in relation to menopause. (source: Mehta2019.md)
• Ever HRT was associated with reduced all-cause, non-cancer and cardiovascular mortality across menopause types regardless of smoking status. (source: Gai2024.md)
• Oral vs transdermal estrogen therapy has differential association with venous thromboembolism risk. (source: Scarabin2003.md)

Perimenopausal Depression

• Guidelines for the evaluation and treatment of perimenopausal depression include recommendations for diagnosis and management. (source: Maki2019.md)

ADHD and Menopause

• Women with ADHD do not experience greater menopausal complaints than women without at any menopausal stage. (source: Chapman2025.md)

Large Language Models (LLMs) and Menopause

• LLMs showed limited accuracy on menopause and hormone therapy questions, with frequent incorrect or incomplete responses. (source: menopause-llm-accuracy-2026-GME002695.md)

Research Library Management

• The ResearchLibrary repository serves as a central source-research repository for validated claims across projects, with PDFs in pdfs/ and one note per DOI in sources/. (source: README.md)
• Every note in sources/ carries a status: field indicating whether it holds just a DOI pointer (index), an abstract (abstract), full text (fulltext), or points to a local PDF (pdf). (source: README.md)
• The library maintains integrity through tools like library_status.py which verifies note contents match their status: declarations. (source: SESSION-HANDOFF-2026-07-15-sources-rename.md)
• A cross-harness handoff protocol (AGENTS.md) ensures consistency across multiple AI coding tools (e.g., Claude Code, Codex, Kilo, Goose) by using the git repo and HANDOFF.md as shared memory. (source: AGENTS.md)

Exogenous Testosterone in Women

• The female free-testosterone reference range rests on a 161-woman study from 2011 or a calculation that method papers say is broken; the equivalent standardized equilibrium-dialysis study that exists for men has never been done in women. (source: HANDOFF.md)
• Testosterone therapy in women (Davis 2008 NEJM, Islam 2019 Lancet D&E) and masculinizing therapy in trans men (Hembree 2017, Greene 2021, Humble 2022, Nolan 2022, ENIGI 2022, Wiepjes 2018, Madsen 2021, Okano 2025) form the exogenous-dosing corpus. (source: HANDOFF.md)
• Supraphysiologic testosterone levels in women arise from three clusters: pellets and implants (Cureus 2025 review documents early peaks of 144 to 299 ng/dL from compounded pellets), self-administering athletes (Malarkey 1991 showed 30-fold elevations, 3 of 9 women above the normal male upper limit, HDL -39%; Havnes 2020 and Frontiers 2021 on irreversible virilization), and state-program doping (Franke & Berendonk 1997, recovered GDR files). (source: HANDOFF.md)
• The 2019 consensus of eleven societies states the evidence is insufficient to claim that testosterone fixes brain fog and energy in women. (source: HANDOFF.md)

Transgender Hormone Therapy and Body Composition

• In trans women (birth-assigned males, female gender identity) receiving estradiol and antiandrogen therapy, total body fat increased by 4.0 kg after 1 year, while visceral fat did not change, resulting in a 17% decrease in the visceral-to-total body fat ratio (VAT/TBF). (source: klaver-2022-fulltext.md)
• In trans men (birth-assigned females, male gender identity) receiving testosterone therapy, total body fat decreased by 2.8 kg after 1 year, while visceral fat did not change, resulting in a 14% increase in the VAT/TBF ratio. (source: klaver-2022-fulltext.md)
• Changes in VAT/TBF were not associated with changes in blood lipids or HOMA-IR (insulin resistance) in either group, suggesting that any unfavorable cardiometabolic effects of hormone therapy are not mediated by changes in visceral fat. (source: klaver-2022-fulltext.md)
• The study, part of the ENIGI project (European Network for the Investigation of Gender Incongruence), used dual-energy X-ray absorptiometry (DXA) to estimate visceral fat in 179 trans women and 162 trans men. (source: klaver-2022-fulltext.md)
• These findings contrast with a smaller 1990s study by Elbers et al that reported increases in visceral fat in both trans women and trans men after hormone therapy. (source: klaver-2022-fulltext.md)
• The study's introduction notes that during menopause, declining estradiol is associated with increased visceral fat, underscoring the role of sex hormones in body fat distribution. (source: klaver-2022-fulltext.md)