{"doi":"10.1210/clinem/dgaf592","title":"Adverse Cardiometabolic Impacts of Sleep Fragmentation and Estradiol Suppression: An Experimental Model of Menopause","abstract":"CONTEXT: Risk of cardiometabolic disease increases in women transitioning to postmenopause, during which estradiol declines universally. Most of these women experience fragmentation of sleep because of nocturnal hot flashes, without a reduction in total sleep time. OBJECTIVE: We examined the independent impact of estradiol suppression, sleep, and their combination on cardiometabolic outcomes categorized as satiety and hunger, lipid profile, cardiac vital signs, and glucoregulation. DESIGN: Participants completed 5-night inpatient studies under eucaloric conditions, once during mid-follicular phase/estrogenized and again under estrogen-suppressed conditions, using the same experimental protocol both times. For all participants, sleep was unfragmented the first 2 nights and then experimentally fragmented without reducing total sleep time the next 3 nights. SETTING: Inpatient intensive physiological monitoring research facility. PARTICIPANTS: Thirty-eight healthy premenopausal women. INTERVENTION(S): Clinical experimental induced menopause model including GnRH agonist-induced hypoestrogenism and sleep fragmentation. MAIN OUTCOME MEASURE(S): Leptin and satiety. RESULTS: Estradiol suppression significantly decreased leptin and increased lipid profiles (false discovery rate [FDR]-adjusted P ≤ .05). Sleep fragmentation significantly increased heart rate (FDR-adjusted P = .002) and trended to increase fasting glucose (FDR-adjusted P = .08). Estradiol suppression and sleep fragmentation worsened individual cardiometabolic outcomes by (median, interquartile range) 4.0% (1.5%, 6.3%) from normalized baseline values. Sleep fragmentation worsened a composite cardiometabolic index derived from individual clinical cardiometabolic measures by an additional 103% over estradiol suppression alone. CONCLUSION: Independent of aging, there are significant adverse changes in cardiometabolic health induced by core components of the transition to postmenopause, including novel effects of sleep fragmentation, a modifiable target.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2025,"id":537111,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":506817,"name":"Leilah K Grant","orcid":"0000-0002-6165-7044","position":1,"is_corresponding":false},{"id":311930,"name":"Aviva Cohn","orcid":"0000-0001-8976-6544","position":2,"is_corresponding":false},{"id":736766,"name":"Jessica Harder","orcid":null,"position":3,"is_corresponding":false},{"id":915077,"name":"Margo Nathan","orcid":"0000-0003-4347-4874","position":4,"is_corresponding":false},{"id":1264572,"name":"Irene Gonsalvez","orcid":null,"position":5,"is_corresponding":false},{"id":736767,"name":"Aleta Wiley","orcid":null,"position":6,"is_corresponding":false},{"id":351263,"name":"Samia Mora","orcid":"0000-0001-6283-0980","position":7,"is_corresponding":false},{"id":447721,"name":"J. Andrew Taylor","orcid":"0000-0003-2802-4330","position":8,"is_corresponding":false},{"id":249994,"name":"Frank A. J. L. Scheer","orcid":"0000-0002-2014-7582","position":9,"is_corresponding":false},{"id":198944,"name":"Elizabeth B. Klerman","orcid":"0000-0002-7402-3171","position":10,"is_corresponding":false},{"id":160512,"name":"Ursula B Kaiser","orcid":"0000-0002-8237-0704","position":11,"is_corresponding":false},{"id":309262,"name":"Sybil L. Crawford","orcid":"0000-0001-6621-0439","position":12,"is_corresponding":false},{"id":284571,"name":"Hadine Joffe","orcid":"0000-0002-7035-8249","position":13,"is_corresponding":false},{"id":342319,"name":"Shadab A. Rahman","orcid":"0000-0002-8729-0500","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:09.056872Z","pmid":"41206010","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}