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Horm Metab Res 2021; 53(08): 520-528
DOI: 10.1055/a-1542-8763
Endocrine Care

Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels

Carla Pelusi
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Flamina Fanelli
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Margherita Baccini
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Giovanni De Pergola
2   Nutrition Outpatient Clinic, Clinical Oncology Unit, University of Bari, Bari, Italy
,
Vincenzo Triggiani
3   Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy
,
Marco Mezzullo
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Alessia Fazzini
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Guido Di Dalmazi
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Biljana Petrovic
4   Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
,
Paola Paterini
4   Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
,
Antonio Maria Morselli Labate
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Uberto Pagotto
1   Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Vito Angelo Giagulli
3   Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy
5   Outpatients Clinic of Endocrinology and Metabolic Disease, Conversano Hospital, Bari, Italy
› Author Affiliations Funding Information Italian Research Project of Relevant Interest (PRIN 2010–2011); Emilia-Romagna Region–University Program grant for Young Investigators “Alessandro Liberati” (PRUA 1–2012–004).
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Abstract

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 17α-hydroxypregnelone (17αOH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17α-hydroxyprogesterone (17αOH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17β-estradiol (E2), 11-deoxycortisol (11 S), 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 17αOH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17αOH-P4/P4, E2/E1, 17αOH-P4/17αOH-P5, A/17αOH-P4, T/A, E1/A, F/11 S, 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 Δ5 rather than the Δ4 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.

Key words

functional hypogonadism - clomiphene citrate - testosterone - cortisol


Publication History

Received: 06 March 2021

Accepted after revision: 24 June 2021

Article published online:
12 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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