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Clinical research

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study

International Journal of Obesityvolume 42pages953963 (2018) | Download Citation

Abstract

Background

Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility.

Objective

To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH).

Design

Single-center, randomized, double-blind, placebo-controlled trial.

Participants

Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire.

Intervention

Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks.

Outcomes

(1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects.

Results

There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function.

Conclusions

CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

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Acknowledgements

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo Grant 2013/16781-1 and Hospital das Clínicas, Universidade de São Paulo.

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Affiliations

  1. Grupo de Obesidade e Síndrome Metabólica, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    • Andressa Heimbecher Soares
    •  & Nidia Celeste Horie
  2. Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    • Lucas Augusto Piccinin Chiang
  3. Unidade de Medicina Interdisciplinar em Cardiologia, INCOR, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil

    • Bruno Caramelli
    •  & Mariana Gomes Matheus
  4. Hospital Israelita Albert Einstein, São Paulo, Brazil

    • Alexandre Holthausen Campos
  5. Experimental Research Center, Hospital Israelita Albert Einstein, São Paulo, Brazil

    • Luciana Cavalheiro Marti
    •  & Fernanda Agostini Rocha
  6. Grupo de Obesidade e Síndrome Metabólica and Laboratory of Carbohydrates and Raioimmunoassay (LIM/18), ICHC, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    • Marcio C. Mancini
    •  & Cintia Cercato
  7. Unidade de Endocrinologia do Desenvolvimento/Hormone and Molecular Genetics Laboratory (LIM/42), ICHC, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    • Elaine Maria Frade Costa

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Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Andressa Heimbecher Soares.

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DOI

https://doi.org/10.1038/s41366-018-0105-2