{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T15:36:36Z","timestamp":1782315396495,"version":"3.54.5"},"reference-count":154,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T00:00:00Z","timestamp":1539475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Throughout history, menopause has been regarded as a transition in a woman\u2019s life. With the increase in life expectancy, women now spend more than a third of their lives in menopause. During these years, women may experience intolerable symptoms both physically and mentally, leading them to seek clinical advice. It is imperative for healthcare providers to improve the quality of life by reducing bothersome menopausal symptoms and preventing disorders such as osteoporosis and atherosclerosis. The current treatment in the form of hormone replacement therapy (HRT) is sometimes inadequate with several limitations and adverse effects. Objective and rationale: The current review aims to discuss the need, efficacy, and limitations of current HRT; the role of other ovarian hormones, and where we stand in comparison with ovary-in situ; and finally, explore towards the preparation of an HRT model by regeneration of ovaries tissues through stem cells which can replicate a functional ovary. Search methods: Four electronic databases (MEDLINE, Embase, Web of Science and CINAHL) were searched from database inception until 26 April 2018, using a combination of relevant controlled vocabulary terms and free-text terms related to \u2018menopause\u2019, \u2018hormone replacement therapy\u2019, \u2018ovary regeneration\u2019, \u2018stem cells\u2019 and \u2018ovarian transplantation\u2019. Outcomes: We present a synthesis of the existing data on the efficacy and limitations of HRT. HRT is far from adequate in postmenopausal women with symptoms of hormone deprivation as it fails to deliver all hormones secreted by na\u00efve ovarian tissue. Moreover, the pharmacokinetics of synthetic hormones makes them substantially different from natural ones. Not only does the number and type of hormones given in HRT matter, but the route of delivering and their release in circulation are also imperative. The hormones are delivered either orally or topically in a non-physiological uniform manner, which brings along with it several side effects. These identify the need for a hormone delivery system which replicates, integrates and reacts as per the requirement of the female body. Wider implications: The review outlines the strengths and weaknesses of HRT and highlights the potential areas for future research. There is a tremendous potential for research in this field to understand the collective roles of the various ovarian hormones and to devise an auto-regulated hormone delivery system which replicates the normal physiology. Its clinical applications can prove to be transformative for postmenopausal women helping them to lead a healthy and productive life.<\/jats:p>","DOI":"10.3390\/ijms19103160","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T03:43:01Z","timestamp":1539574981000},"page":"3160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary?"],"prefix":"10.3390","volume":"19","author":[{"given":"Swati","family":"Agarwal","sequence":"first","affiliation":[{"name":"Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK"},{"name":"Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5S 3H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-4000","authenticated-orcid":false,"given":"Faisal A","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia, <email>faahalzahrani@kau.edu.sa<\/email>"},{"name":"Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK"},{"name":"Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,14]]},"reference":[{"key":"ref_1","unstructured":"Jameson, J.L., de Kretser, D.M., Marshall, J.C., and De Groot, L.J. 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