{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:33:34Z","timestamp":1792802014517,"version":"4.5.0"},"reference-count":52,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100026321","name":"Louis B. Mayer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100026321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edythe L. Broad Women\u2019s Heart Research Fellowship"},{"name":"Barbra Streisand Women\u2019s Cardiovascular Research and Education Program"},{"name":"Smidt Heart Institute"},{"DOI":"10.13039\/100013015","name":"Cedars-Sinai Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013015","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mayo Clinic Women\u2019s Health Research Center","id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Endothelial dysfunction and altered psychological measures have been identified in women with functional hypothalamic amenorrhea (FHA). Estradiol (E2) replacement, a known vasodilator, may potentially reverse vascular dysfunction and improve psychological health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate 12 weeks of physiologic E2 replacement on vascular, hormonal, and psychological outcomes in women with FHA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled trial was conducted in 29 women with FHA with 0.1\u2005mg\/day transdermal E2 (n = 14) or placebo patch (n = 15) twice weekly for 12 weeks. FHA was defined as amenorrhea \u22653 consecutive months, E2 &amp;lt; 50\u2005pg\/mL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) &amp;lt;10\u2005mIU\/L, LH:FSH &amp;lt;1, excluding other etiologies. Endothelial dysfunction (reactive hyperemic index \u2264 1.67) was assessed, as were hormonal and psychological measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Women with FHA had a mean age of 26.2 \u00b1 6.3 years, body mass index of 21.5 \u00b1 3.3\u2005kg\/m2, with 63% being non-Hispanic White. Baseline characteristics did not differ between groups. After 12 weeks, E2 levels were significantly higher in the E2 group (112.0 vs 36.5\u2005pg\/mL, P = .0002). However, there were no significant differences in vascular, hormonal, or psychological outcomes between E2 and placebo groups at week 12. Cortisol levels showed a near-significant decrease in the E2 group compared to an increase with placebo (\u2212.4 vs 3.1\u2005\u00b5g\/dL, P = .05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In women with FHA, 12 weeks of transdermal E2 increased serum E2 levels but did not improve vascular or psychological health measures. Further studies with larger sample sizes and longer follow-up are needed to explore the long-term effects of E2 therapy on cardiovascular and mental health outcomes in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf364","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T07:53:45Z","timestamp":1750233225000},"page":"e552-e559","source":"Crossref","is-referenced-by-count":4,"title":["Impact of Estrogen Replacement on Endothelial Dysfunction and Psychological Health in Women With Hypothalamic Amenorrhea"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6886-9210","authenticated-orcid":false,"given":"Chrisandra L","family":"Shufelt","sequence":"first","affiliation":[{"name":"Division of General Internal Medicine, Mayo Clinic , Jacksonville, FL 32224 ,","place":["USA"]},{"name":"Mayo Clinic Center for Women's Health , Rochester, MN 55905 ,","place":["USA"]},{"name":"Women's Health Research Center, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Safwan","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Mayo Clinic , Jacksonville, FL 32224 ,","place":["USA"]},{"name":"Mayo Clinic Center for Women's Health , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Saadedine","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, Mayo Clinic , Jacksonville, FL 32224 ,","place":["USA"]},{"name":"Mayo Clinic Center for Women's Health , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen","family":"Cook-Wiens","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Maughan","sequence":"additional","affiliation":[{"name":"Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta D","family":"Pisarska","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7595","authenticated-orcid":false,"given":"JoAnn E","family":"Manson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T. 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