Sex Difference in the Relationship between the Hypothalamic-pituitary-adrenal Axis and Sex Hormones in Obesity

Authors

  • Valentina Vicennati,

    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
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  • Luana Ceroni,

    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
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  • Silvia Genghini,

    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
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  • Laura Patton,

    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
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  • Uberto Pagotto,

    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
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  • Renato Pasquali

    Corresponding author
    1. Division of Endocrinology, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Bologna, Italy
      Unità Operativa di Endocrinologia, Dipartimento di Medicina Interna, Az. Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. E-mail: renato.pasquali@unibo.it
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  • The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Unità Operativa di Endocrinologia, Dipartimento di Medicina Interna, Az. Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. E-mail: renato.pasquali@unibo.it

Abstract

Objective: This study was carried out to investigate the role of sex in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its relationship with testosterone levels in male and female obesity.

Research Methods and Procedures: Twenty-two obese men (OB-M) and 29 obese women (OB-W) participated in the study. Two groups of normal weight men (NW-M) and women (NW-W), respectively, served as controls. In basal conditions, blood concentrations of major androgens, sex hormone—binding protein, and gonadotropins were assessed, and the free androgen index (testosterone ×100/ sex hormone-binding globulin) was calculated. All subjects underwent a combined corticotropin-releasing hormone plus arginine-vasopressin stimulation test.

Results: OB-M and NW-M had higher basal adrenal cortical tropic hormone (ACTH) and cortisol levels than their female counterparts. In addition, ACTH, but not cortisol basal, levels were significantly higher in obese than in normal weight controls in both sexes. OB-W had a higher response than OB-M to the combined corticotropin-releasing hormone plus arginine-vasopressin test of both ACTH and cortisol [expressed as incremental percentage of area under the curve (AUC%)]. The same finding was present between NW-W and NW-M. Basal luteinizing hormone levels were negatively correlated to ACTHAUC% in both OB-W and OB-M. In the OB-W, however, a positive correlation was found between cortisolAUC% and testosterone (r = 0.48; p = 0.002), whereas a tendency toward a negative correlation was present in OB-M.

Discussion: In conclusion, we have shown a significant positive relationship between the activity of the HPA axis and testosterone in obese women, which suggests a partial responsibility of increased HPA axis activity in determining testosterone levels. In addition, it clearly seems that, as reported in normal weight subjects, a sex difference in the HPA axis activity still persists even in the presence of obesity.

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