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Multidisciplinary Insights Into the Assessment, Diagnosis, and Management of Hypogonadism

Figure 2. Mechanism of Action of Testosterone and Its Effects on Many Different Body Tissues, Systems, and Clinical Outcomes9

Adapted with permission.

Figure 3. Testosterone and Its Metabolites Have Physiologic Effects on Many Organs8

• CNS (libido, energy, well-being, spatial cognition) • Hypothalamus/pituitary (GnRH, LH, FSH;GH) • Larynx (lowers voice) • Breast (E2size) • Liver (SHBG, HDL) • Kidney (erythropoietin) • Genitals (suppression of spermatogenesis, erections)

• Prostate (size, secretions) • Skin (facial/body hair, sebum production) • Bone (BMD) • Muscle (lean mass, strength) • Adipose tissue (lipolysis,abdominal fat) • Blood (hematocrit) • Immune system (auto-antibody production)

B M D , b o n e m i n e r a l d e n s i t y ; C N S , c e n t r a l n e r v o u s s y s t e m ; E 2 , e s t r a d i o l ; F S H , f o l l i c l e - s t i m u l a t i n g h o r m o n e ; G H , g r o w t h h o r m o n e ; G n R H , g o n a d o t r o p i n - r e l e a s i n g h o r m o n e ; H D L , h i g h - d e n s i t y l i p o p r o t e i n ; L H , l u t e i n i z i n g h o r m o n e SHBG, sex hormone-binding globulin. ;

Free testosterone index =

Testosterone SHBG

The major androgens in the circulation are testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone and its sulfate, with testosterone being the most important biologically.10 Testosterone is metabolized into DHT and estradiol through 5α-reductase and aromatase, respectively.

Fear prevailing about the use of hormones and their potential negative effects is driven in part by data regarding the risks of hormone supplementation in women. Martin M. Miner, MD, Clinical Associate Professor of Family Medicine at the Warren Alpert School of Medicine of Brown University in Providence, Rhode Island, has stated that it is important for clinicians to be aware, and to educate their patients, that the

goal of hormone therapy is to reestablish normal physiologic levels of serum testosterone.

Comorbid conditions

Because primary care physicians see men with a variety of health issues, it is important to be aware of other medical conditions and how they can affect or be affected by testosterone levels (Table 1).10 Several medications can cause levels of testosterone to decrease, including gonadotropin-releasing hormone agonists and antagonists, estrogens and progestins, glucocorticoids, ketoconazole, aldactone, thiazide diuretics, opiates, anabolic steroids, amiodarone, and psychotropic agents.10 Aldactone, cimetidine, flutamide, and androgen antagonists also impair testosterone activity at the receptor.11

Table 1. Conditions and Medications That Can Cause Hypogonadism10 Acute Critical Illness Chronic Systemic Diseases Type 2 diabetes Chronic obstructive pulmonary disease Chronic liver disease Chronic renal failure Endocrine diseases Surgical trauma Myocardial infarction

  • Primary testicular lesions

  • Cushing syndrome

  • Prolactinoma and other tumors

Sickle cell disease


GnRH analogs Antiandrogens Alkylating agents Systemic glucocorticoids Opiates Cannabinoids Neuroleptic drugs

GnRH, gonadotropin-releasing hormone.


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