Testosterone, Hypogonadism and Male Sexual Health

The axis this whole chapter runs on

You do not need to re-learn the hormones — only to apply the loop. The Endocrine section teaches the hypothalamic–pituitary–gonadal (HPG) axis in full: the hypothalamus releases GnRH in pulses, the pituitary answers with LH and FSH, and in the testis LH drives the Leydig cells to make testosterone while FSH (with local testosterone) drives the Sertoli cells to make sperm. Testosterone then feeds back negatively on the hypothalamus and pituitary to keep itself in range. Almost every clinical decision in male health is just this loop read forwards or backwards. Give testosterone from outside and the loop reads it as "enough" — GnRH, LH and FSH fall, and the testis stops both its own production and, critically, sperm-making. Hold that single fact and the rest of this article follows.

Primary vs secondary hypogonadism — one blood test splits them

Hypogonadism means the testis is not delivering enough testosterone — but the where of the failure changes everything. In primary hypogonadism the fault is in the testis itself (Klinefelter syndrome, mumps orchitis, trauma, chemotherapy, castration). The gland is deaf; the pituitary shouts louder and louder, so LH and FSH are HIGH — hypergonadotropic hypogonadism. In secondary (central) hypogonadism the fault is upstream, in the hypothalamus or pituitary (a pituitary tumour, hyperprolactinaemia, opioids, Kallmann syndrome, or simply chronic illness and obesity). The command is never sent, so LH and FSH are LOW or inappropriately normal — hypogonadotropic hypogonadism. That single pair of numbers — low testosterone with high gonadotropins versus low testosterone with low gonadotropins — localises the lesion before any imaging. It also decides treatment: primary failure can only be replaced; secondary failure can sometimes be driven back to life.

Diagnose before you prescribe — and diagnose properly. Testosterone follows a diurnal rhythm, peaking in the morning, so the diagnosis rests on a morning (fasting, 8–11 am) total testosterone that is genuinely low, confirmed on a repeat sample on a separate day — a single low reading, especially one taken in the afternoon or during acute illness, means very little. Symptoms must accompany the biochemistry: low libido, erectile dysfunction, fatigue, loss of morning erections, reduced muscle and body hair. Only once you have low symptoms plus two low morning levels do you measure LH and FSH to place the lesion, add prolactin and iron studies to hunt a cause, and consider pituitary imaging if the picture is central. Skipping these steps is how men end up on lifelong testosterone they never needed.

Testosterone replacement therapy — for the genuinely deficient only

In confirmed hypogonadism, testosterone replacement therapy (TRT) restores libido, energy, muscle mass, bone density and mood, and the aim is simple: return the level to the physiological mid-normal range, not to push it higher. Formulations differ mainly in how they deliver: topical gels applied daily to the skin give smooth, steady levels but carry a distinctive hazard — transference. The hormone can rub off onto a partner or, worse, a child through skin contact, causing virilisation, so the site must be covered and washed. Long-acting intramuscular injections (testosterone undecanoate every 10–14 weeks, or shorter esters) are convenient and avoid transference but can produce peaks and troughs. Crucially, TRT is a treatment for disease, not for the normal, gradual, modest fall of testosterone with age — prescribing it for ordinary ageing exposes a man to all the risks below for no proven benefit.

The monitoring TRT demands

Every adverse effect of testosterone is an amplified version of what it does normally. Testosterone stimulates erythropoiesis, so it can raise the haematocrit into frank polycythaemia — thick blood that risks stroke and thrombosis. A full blood count / haematocrit is checked at baseline, then at intervals; a haematocrit above threshold means dose reduction or venesection. (This is the same testosterone-driven erythropoiesis the Haematology section invokes to explain why men run higher haemoglobin than women.) Testosterone is fuel for the prostate: it can worsen benign prostatic symptoms and can unmask or accelerate an occult prostate cancer, so prostate assessment and a baseline and follow-up PSA are mandatory — an unexplained PSA rise stops the drug and prompts urological referral (see the Prostate / BPH chapter). It suppresses spermatogenesis via the negative feedback above, causing infertility — so it is the wrong drug for any man who wants children. Other effects to watch: fluid retention, acne, gynaecomastia (from aromatisation to oestrogen), worsening of sleep apnoea, and a long-debated, still-unsettled cardiovascular signal. TRT is absolutely contraindicated in prostate cancer and male breast cancer, both hormone-driven tumours.

The abuse problem: anabolic–androgenic steroids

Away from the clinic, testosterone and its synthetic cousins are misused on a large scale for muscle-building and doping — a genuine clinical problem, not a curiosity. Users take supraphysiological doses, many times any replacement dose, and the harms are the adverse-effect list turned up to full volume. The suppressed axis shrinks the testes and causes infertility; excess androgen aromatises to oestrogen and produces gynaecomastia; there is acne, oily skin, and prominent mood disturbance — irritability, aggression ("roid rage"), and dependence. Systemically, they drive an adverse lipid profile and hypertension with a real cardiovascular toll (cardiomyopathy, arrhythmia), and oral 17-alpha-alkylated agents are hepatotoxic (cholestasis, tumours). A crucial teaching point: when such a man later wants children, the treatment is the same axis-restarting strategy used for secondary hypogonadism — and it can take many months for the pituitary to wake up, if it fully does at all.

Male infertility: driving the axis, not flooding it

The fertility problem is where the feedback logic pays off completely. For a man with secondary (hypogonadotropic) hypogonadism who wants to conceive, the goal is to make the testis work, and that means supplying the signals it is missing — never the finished hormone, which would suppress the axis further. Give gonadotropins: hCG mimics LH to drive the Leydig cells (raising intratesticular testosterone), and recombinant or purified FSH is added to drive the Sertoli cells and stimulate spermatogenesis. Where the pituitary is intact but the hypothalamus fails (as in Kallmann syndrome), pulsatile GnRH delivered by pump can restart the whole cascade physiologically. Off-label, clomifene (a selective oestrogen-receptor modulator that blocks negative feedback and lifts the man's own LH/FSH) and aromatase inhibitors (which cut oestrogen feedback) are used to raise endogenous testosterone while preserving fertility. Primary testicular failure, by contrast, cannot be driven — the gland is deaf — and idiopathic or varicocele-associated infertility is managed differently. The gonadotropin approach is developed further in the Fertility chapter.

Premature ejaculation: borrowing an SSRI side effect

Premature ejaculation is the commonest male sexual complaint, and its pharmacology is a neat case of turning a drug's nuisance into its purpose. Delayed ejaculation is a well-known class effect of selective serotonin reuptake inhibitors (SSRIs) — raising synaptic serotonin lengthens the time to ejaculation. Dapoxetine is a short-acting SSRI designed and licensed specifically for this: taken on-demand a few hours before intercourse, its rapid absorption and clearance suit episodic use. Where dapoxetine is unavailable, daily off-label paroxetine or sertraline exploit the same class effect (see the Central Nervous System section for full SSRI pharmacology). Topical local anaesthetics (lidocaine/prilocaine cream or spray) reduce glans sensitivity as a simple mechanical adjunct, and PDE5 inhibitors can be added — particularly where erectile dysfunction coexists, tying this back to the Erectile dysfunction chapter and its central safety rule: never combine a PDE5 inhibitor with nitrates.