Secondary Hypogonadism (Low LH): Causes and Diagnosis

The hypothalamus releases GnRH in pulses — every few dozen minutes. This rhythm stimulates the pituitary to secrete LH and FSH, and LH in turn stimulates Leydig cells in the testes to make testosterone. Testosterone (and the estradiol formed from it) returns to the hypothalamus and pituitary, suppressing further secretion. This arrangement is a 'thermostat': when testosterone falls, LH normally rises to push it up. If LH does not rise despite low testosterone, the 'sensor' or 'relay' in the hypothalamus or pituitary is switched off or dampened.

That is why in a man with low testosterone LH (and FSH) must always be measured. A high result points to the testes, a low or normal one to the 'upper' part of the axis. A 'normal' result is a trap here: with low testosterone the 'normal' range for LH is inappropriate. LH in the lower half of the range, or even mid-range, may be insufficient with testosterone below normal, which laboratories rarely emphasize. The pair is assessed, not a single parameter.

An important distinction is between organic hypogonadism (structural or genetic damage of the axis) and functional hypogonadism (the axis is intact but 'braked' by general condition, drugs or metabolism). The distinction is key because functional can be reversible, and treating testosterone alone does not remove its cause — and additionally suppresses the man's own axis and fertility.

This list is best read as a list of 'first things to check'. Before a man with low LH is sent for a pituitary MRI, body weight and waist circumference, glycemia and HbA1c, medications (including painkillers), sleep and prolactin are analyzed. In practice most cases of secondary hypogonadism in adult men have a functional basis, not a tumor.

A 2025 review summarizes that opioids suppress the gonadal axis mainly by suppressing GnRH synthesis and secretion, and that chronic use is a common but underappreciated cause of androgen deficiency in men. The authors call for greater awareness among doctors and consider testosterone in men with unequivocal deficiency after thorough clinical assessment.

In practice: if you take opioids (including tramadol, codeine, buprenorphine) and have low libido, fatigue or erectile problems, it is worth testing testosterone and LH — and raising the issue with the doctor managing your pain treatment. Stopping the drug is not always possible, and decisions about replacement therapy are made by the doctor after weighing benefits and risks. A similar logic applies to other drugs affecting the axis: glucocorticoids, some neuroleptics (which raise prolactin) and anabolic steroids.

Prolactin is the only pituitary hormone mostly inhibited (by dopamine) rather than stimulated. When it is raised it can suppress GnRH secretion and lower LH and testosterone. The 2011 Endocrine Society guideline describes assessing the causes of hyperprolactinemia, managing drug-induced hyperprolactinemia and treating prolactinomas; the basis is to establish whether high prolactin is due to a drug, hypothyroidism, kidney failure, a tumor, or an artifact (macroprolactin, stress at sampling).

In a man with low LH and testosterone, prolactin should always be measured. A result only slightly raised more often has a drug-related or functional cause, whereas a result many times above the upper limit (above twice the upper limit of normal in the study we describe below) raises the likelihood of a pituitary adenoma and is an indication for MRI. We write about interpreting prolactin in more detail in the knowledge base, and about high prolactin without a tumor in one of the next publications.

Data from a single center, a small group and from twenty years ago cannot be regarded as a guideline, but they illustrate an important principle: in a typical population of men with low testosterone and low LH, MRI very rarely detects a significant lesion, and the best predictor of an adenoma was clearly raised prolactin. That does not mean MRI is never needed — it can be essential when the picture is atypical.

Among organic causes the most common are pituitary adenomas (prolactinoma and non-functioning macroadenomas, which compress healthy pituitary tissue), empty sella, pituitary inflammation, head injury or hemorrhage, radiotherapy and surgery near the pituitary, infiltrative diseases (sarcoidosis, histiocytosis) and iron-overload diseases such as hemochromatosis and thalassemia. Reports from referral centers show that iron overload can damage the hypothalamic–pituitary–testicular axis and contribute to hypogonadism — which is why, with unexplained deficiency, especially with diabetes, joint pain or skin changes, ferritin and transferrin saturation are sometimes part of the workup.

A separate group is idiopathic hypogonadotropic hypogonadism (IHH), including Kallmann syndrome (with a disorder of smell), caused by a congenital disorder of GnRH secretion. It usually shows up as delayed or absent puberty, but diagnosis in adults does occur. A retrospective study of 308 patients with IHH found that 44 underwent 'reversal' — spontaneous activation of the axis with normalization of steroidogenesis or gametogenesis; the estimated lifetime incidence of reversal was 22%. This shows that even congenital hypogonadism is not always permanent and that follow-up after stopping treatment makes sense.

The rule is: cause first, hormone second. In obesity and diabetes the basis is weight loss and better metabolic control. A 2026 umbrella review of reviews indicates that weight-lowering interventions improve the sex hormone profile in men with obesity — most strongly and consistently bariatric surgery (an increase in total testosterone of up to 8.7 nmol/l and in SHBG, and also LH and FSH), less so dietary changes; the quality of evidence varies.

With hyperprolactinemia its cause is treated — the offending drug is stopped or changed, the thyroid corrected, and in a prolactinoma dopaminergic drugs are used according to guidelines. In drug-related hypogonadism (opioids) modification of pain therapy is considered, and testosterone only after thorough assessment. In men with organic pituitary damage, deficiencies of other hormones (cortisol, thyroxine) are usually treated too, which takes precedence over testosterone.

If testosterone deficiency persists and symptoms are marked, a doctor may propose testosterone therapy — remembering that it suppresses LH, FSH and spermatogenesis. In men planning a child other strategies are used, such as hCG (with or without FSH) or estrogen receptor modulators; we describe them in separate material on testosterone therapy and fertility. The Endocrine Society guideline advises against starting testosterone therapy in men who plan a child in the near term.

A second common misunderstanding concerns treatment: 'since it is secondary, it is enough to raise LH'. LH is not a first-choice drug, and no supplement or 'booster' replaces removing the cause. In principle the cause is treated, and hormones are used by indication and with parenthood plans taken into account.

Low LH with low testosterone is sometimes perceived as a harbinger of serious pituitary disease and less often as what it most commonly is: a signal that the body has 'braked' the reproductive axis because of weight, drugs, sleep or metabolism. The good news is that many of these causes can be identified with inexpensive tests and a conversation with a doctor. The bad — that reaching quickly for testosterone postpones this workup and additionally switches off the man's own axis.