Hypogonadism Diagnosis and Treatment

Introduction to Hypogonadism

The National Comprehensive Cancer Network recommends that a patient with normal LH and FSH levels but low testosterone does not have primary hypogonadism, but rather has secondary hypogonadism or adult-onset hypogonadism 1, 2

Primary hypogonadism (hypergonadotropic) is caused by testicular dysfunction with low testosterone levels and elevated LH and FSH levels above normal as a compensatory response, according to the European Urology guidelines 1, 3
Secondary hypogonadism (hypogonadotropic) results from impairment of the hypothalamic-pituitary-gonadal axis with low testosterone and normal or low LH and FSH levels, as stated by the National Comprehensive Cancer Network 1, 2

Normal LH/FSH with low testosterone indicates secondary hypogonadism or adult-onset hypogonadism, based on the National Comprehensive Cancer Network guidelines 1, 2

Obesity is a cause of secondary hypogonadism due to increased aromatization of testosterone to estradiol in adipose tissue, with subsequent estradiol-mediated negative feedback suppressing pituitary LH secretion, according to Gastroenterology research 4
Medications such as opiates, GnRH agonists/antagonists, glucocorticoids, estrogens, and progestogens can cause secondary hypogonadism, as reported by the European Urology journal 5

The Gastroenterology guidelines recommend confirming low testosterone with repeat morning measurements (between 8-10 AM) 4
Measuring free testosterone by equilibrium dialysis is recommended, especially in obese patients, according to the Gastroenterology journal 4
Checking sex hormone-binding globulin levels is necessary, as low levels can affect total testosterone measurements, as stated by the Gastroenterology research 4

The European Urology guidelines state that secondary hypogonadism patients can potentially achieve both fertility and normal testosterone levels with appropriate treatment 5
Primary hypogonadism patients can only receive testosterone therapy, which compromises fertility by suppressing the HPG axis, according to the European Urology journal 5
The Journal of Urology recommends that testosterone monotherapy should not be prescribed for men interested in fertility, as it can suppress spermatogenesis 6
Treatment options for secondary hypogonadism may include lifestyle modifications for obesity-related hypogonadism, as reported by the European Urology journal 5
Gonadotropin therapy (hCG, FSH) is recommended for those desiring fertility, according to the European Urology and Journal of Urology guidelines 5, 6

The European Association of Urology recommends diagnosing secondary hypogonadism by confirming low morning testosterone (<10.5 nmol/L or ~300 ng/dL) on at least two separate occasions combined with low or inappropriately normal LH/FSH levels, along with specific symptoms of testosterone deficiency 7, 8
Sexual symptoms of secondary hypogonadism include reduced frequency of sexual intercourse, decreased masturbation, and delayed ejaculation, as noted by the European Urology association 7
Physical symptoms of secondary hypogonadism include hot flushes, decreased energy, and reduced physical strength/function/activity, according to the European Urology guidelines 7
Cognitive symptoms of secondary hypogonadism include concentration difficulties, memory problems, and sleep disturbances, as reported by the European Urology association 7

For men not seeking fertility, the European Urology association suggests that lifestyle modifications, such as weight loss through low-calorie diets and physical activity, can be combined with testosterone therapy to reverse obesity-associated secondary hypogonadism 8
For men seeking fertility, the European Urology guidelines recommend gonadotropin therapy, as testosterone therapy is contraindicated due to its suppression of spermatogenesis 8, 9
Combined hCG and FSH therapy provides optimal outcomes for men seeking fertility, as it maintains testosterone levels while preserving fertility, according to the European Urology association 8, 9

The European Urology association states that men desiring fertility are absolute contraindications to testosterone therapy, as it suppresses spermatogenesis 8, 9
Testosterone therapy is recommended as first-line for mild erectile dysfunction, but should not be used for eugonadal men, weight reduction, or cardiometabolic improvement as primary goal, according to the European Urology guidelines 9