{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T00:13:11Z","timestamp":1725667991581},"reference-count":50,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"name":"Italian Research Project of Relevant Interest","award":["PRIN 2010\u20132011"],"award-info":[{"award-number":["PRIN 2010\u20132011"]}]},{"name":"Emilia-Romagna Region\u2013University Program grant for Young Investigators \u201cAlessandro Liberati\u201d","award":["PRUA 1\u20132012\u2013004"],"award-info":[{"award-number":["PRUA 1\u20132012\u2013004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis. The aim of this sub-study was to better understand the changes in steroid levels and metabolism induced by CC treatment. We assessed 17\u03b1-hydroxypregnelone (17\u03b1OH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17\u03b1-hydroxyprogesterone (17\u03b1OH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17\u03b2-estradiol (E2), 11-deoxycortisol (11\u2009S), cortisol (F), and cortisone (E) by LC-MS\/MS, and corticosteroid binding globulin (CBG) by ELISA, before and after each treatment. In addition, free-F and steroid product\/precursor ratios were calculated. We observed a significant change in serum levels induced by CC compared with placebo for 17\u03b1OH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17\u03b1OH-P4\/P4, E2\/E1, 17\u03b1OH-P4\/17\u03b1OH-P5, A\/17\u03b1OH-P4, T\/A, E1\/A, F\/11\u2009S, and F\/E ratios. Therefore, besides the CC stimulating effect on testis steroidogenesis, our study showed increased F, E, but not free-F, levels, indicating changes in steroid metabolism rather than adrenal secretion stimulation. The steroid profiling also revealed the CC stimulation of the \u03945 rather than the \u03944 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.<\/jats:p>","DOI":"10.1055\/a-1542-8763","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T22:48:41Z","timestamp":1628808521000},"page":"520-528","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels"],"prefix":"10.1055","volume":"53","author":[{"given":"Carla","family":"Pelusi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flamina","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Baccini","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"De Pergola","sequence":"additional","affiliation":[{"name":"Nutrition Outpatient Clinic, Clinical Oncology Unit, University of Bari, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Triggiani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Mezzullo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Fazzini","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Di Dalmazi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biljana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Paterini","sequence":"additional","affiliation":[{"name":"Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Maria Morselli","family":"Labate","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito Angelo","family":"Giagulli","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy"},{"name":"Outpatients Clinic of Endocrinology and Metabolic Disease, Conversano Hospital, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/jc.2018-00229","article-title":"Testosterone therapy in men with hypogonadism: an Endocrine Society Clinical Practice Guideline","volume":"103","author":"S Bhasin","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1210\/jc.2016-3580","article-title":"Perspective on middle-aged and older men with functional hypogonadism: focus on holistic management","volume":"102","author":"M 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