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

Carla Pelusi; Flamina Fanelli; Margherita Baccini; Giovanni De Pergola; Vincenzo Triggiani; Marco Mezzullo; Alessia Fazzini; Guido Di Dalmazi; Biljana Petrovic; Paola Paterini; Antonio Maria Morselli Labate; Uberto Pagotto; Vito Angelo Giagulli

doi:10.1055/a-1542-8763

Hormone and Metabolic Research, Table of Contents

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

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Flamina Fanelli

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Margherita Baccini

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Giovanni De Pergola

²Nutrition Outpatient Clinic, Clinical Oncology Unit, University of Bari, Bari, Italy

,

Vincenzo Triggiani

³Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy

,

Marco Mezzullo

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Alessia Fazzini

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Guido Di Dalmazi

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Biljana Petrovic

⁴Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

,

Paola Paterini

⁴Center for Applied Biomedical Research, Department of Medical & Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

,

Antonio Maria Morselli Labate

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Uberto Pagotto

¹Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

,

Vito Angelo Giagulli

³Interdisciplinary Department of Medicine, Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari, Bari, Italy

⁵Outpatients Clinic of Endocrinology and Metabolic Disease, Conversano Hospital, Bari, Italy

› Author Affiliations

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

Full Text

References

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