Appearance
15.2 — Sperm Production and the Male Hormonal Axis
A man produces around 1,000 sperm per second — roughly 100 to 200 million a day, continuously, from puberty until death. Over a lifetime that is well over a trillion.
A woman is born with all the eggs she will ever have (Chapter 15.4).
That asymmetry — continuous manufacture versus a fixed stock laid down before birth — explains most of the differences between male and female reproductive biology, including why paternal age raises the rate of new mutations while maternal age raises the rate of chromosomal errors (Chapter 2.5).
The process
Spermatogenesis takes about 64 to 74 days from stem cell to mature sperm, plus another 2 to 12 days maturing in the epididymis.
Which produces the single most useful practical fact in male fertility: anything affecting sperm production shows up in a semen sample about three months later, and any improvement takes three months to appear.
So a man who stops smoking, treats a fever, or corrects a hormone problem must wait a full cycle before retesting — and a semen analysis taken during or shortly after an illness may be misleadingly poor.
The stages:
Spermatogonia — stem cells at the outer edge of the seminiferous tubule. They divide continuously, one daughter remaining a stem cell and the other committing to sperm production. This is what makes the supply inexhaustible.
Primary spermatocytes — which enter meiosis I (Chapter 1.7).
Secondary spermatocytes — after meiosis I, now haploid.
Spermatids — after meiosis II. Four from each original cell.
Spermatozoa — after a dramatic remodelling called spermiogenesis, in which the round spermatid is converted into a streamlined cell.
And that remodelling is worth describing, because the resulting cell is unlike any other in the body.
The nucleus condenses to a fraction of its former volume, with the DNA packed by small proteins far more tightly than histones allow (Chapter 2.4).
The acrosome forms — a cap of enzymes over the head, for penetrating the egg's coverings (Chapter 4.3).
A flagellum grows, with mitochondria wrapped in a spiral around its base to power it.
And almost all the cytoplasm is discarded, phagocytosed by Sertoli cells.
The result is about 50 to 60 micrometres long, of which the head is only 5, and it is essentially a delivery vehicle for DNA with a fuel supply and a motor.
It swims at around 1 to 4 millimetres per minute — which, for a cell 5 micrometres wide, is a substantial speed relative to its size, and it must be, given the journey in Chapter 4.3.
And a point that surprises people: the mitochondria in the midpiece are destroyed after fertilisation, which is why mitochondrial DNA is inherited only from the mother (Chapter 1.5).
The Sertoli cells
They are the nurse cells, and they do more than support.
They form the blood–testis barrier (Chapter 15.1).
They physically support the developing sperm, which are embedded in deep folds of the Sertoli cell membrane and move progressively toward the lumen as they mature.
They phagocytose the discarded cytoplasm and any defective cells.
They produce androgen-binding protein, which holds testosterone at very high concentration inside the tubule — around 100 times blood levels, which is what spermatogenesis requires.
And they produce inhibin, which feeds back to the pituitary to suppress FSH.
Which means the number of Sertoli cells sets the ceiling on sperm production. Their number is fixed during childhood and early puberty, so anything impairing testicular development in childhood permanently limits adult fertility.
The hormonal axis
Hypothalamus → GnRH (pulsatile) → pituitary → LH and FSH → testis (Chapter 12.6).
And the two pituitary hormones have separate targets, which is unusually clean.
LH acts on Leydig cells → testosterone.FSH acts on Sertoli cells → support for spermatogenesis.
Feedback:
Testosterone suppresses both GnRH and LH.Inhibin, from Sertoli cells, suppresses FSH specifically.
So the system has two independent feedback loops — one reporting on testosterone production and one on sperm production — and they can be read separately.
Which makes the hormone profile diagnostic:
Low testosterone with high LH and FSH — the testis is failing and the pituitary is shouting. Primary testicular failure.
Low testosterone with low or normal LH and FSH — the pituitary or hypothalamus is failing. Secondary hypogonadism.
Normal testosterone with high FSH and low sperm count — the Leydig cells are fine and the Sertoli cell compartment is failing. A specific and informative pattern in male infertility.
And this is why taking testosterone suppresses fertility (Chapter 12.6). Exogenous testosterone suppresses LH and FSH, so the testis stops making its own — and the intratesticular concentration, which needs to be 100 times higher than blood, collapses.
A man on testosterone has a normal blood level and a testis that has effectively been switched off. Sperm counts fall to zero in a majority within a few months, which is why testosterone has been studied as a male contraceptive, and why men on testosterone for symptoms are frequently distressed to discover it later.
Recovery after stopping usually takes 6 to 18 months and is occasionally incomplete.
A man wanting both testosterone effects and fertility needs a different approach — hCG, which mimics LH and stimulates the testis directly, or clomifene, which blocks feedback and raises the body's own LH.
Semen analysis
The primary test of male fertility, and it is worth knowing how to interpret it because it is so often over-interpreted.
Reference values (WHO, lower reference limits):
| Parameter | Lower limit |
|---|---|
| Volume | 1.4 ml |
| Concentration | 16 million/ml |
| Total count | 39 million |
| Total motility | 42% |
| Progressive motility | 30% |
| Normal morphology | 4% |
| Vitality | 54% |
And the crucial point: these are not thresholds for fertility. They are the fifth centile of men who achieved a pregnancy within a year. So a man below them can father children, and a man above them may not.
Semen quality varies enormously between samples from the same man, which is why abnormal results are repeated after at least 6 to 12 weeks before any conclusion is drawn.
Collection matters: after 2 to 7 days of abstinence, the whole sample collected — the first fraction contains most of the sperm — and examined within an hour.
Terminology:
Oligozoospermia — low count. Asthenozoospermia — poor motility. Teratozoospermia — abnormal forms. Azoospermia — no sperm at all.
And azoospermia divides into two categories with completely different management.
Obstructive — production is normal, the plumbing is blocked. Normal testicular size, normal FSH. Sperm can be retrieved surgically and used for IVF with ICSI (Chapter 4.3), with good results.
Non-obstructive — production has failed. Small testes, high FSH. Retrieval is possible in some cases and success rates are much lower.
Distinguishing the two determines everything that follows, and it is done with hormones, examination and sometimes genetic testing.
Causes of male infertility
Male factors contribute to around 40 to 50 percent of infertility, which is worth stating plainly because investigation has historically focused disproportionately on women.
And a semen analysis is cheap, non-invasive and immediate, which makes it one of the first tests rather than one of the last.
Testicular causes:
Varicocele — present in around 15 percent of all men and 40 percent of infertile men. Repair improves semen parameters and its effect on pregnancy rates is debated, with benefit clearest for clinically palpable varicoceles with abnormal semen.
Undescended testis (Chapter 15.1).
Infection — mumps orchitis after puberty damages the testes in around 30 percent of affected men and can cause permanent infertility. Which is one of several reasons the MMR vaccine matters beyond measles (Chapter 13.5).
Trauma, torsion, and testicular cancer treatment.
Genetic causes:
Klinefelter syndrome (47,XXY) — present in about 1 in 600 male births, and found in around 10 percent of men with azoospermia. Frequently undiagnosed until fertility is investigated (Chapter 1.7).
Y chromosome microdeletions — deletions in specific regions of the Y required for spermatogenesis, found in around 5 to 10 percent of men with severe oligozoospermia or azoospermia.
And these are worth testing for, because a Y microdeletion will be passed to any son conceived by ICSI, who will have the same problem.
Cystic fibrosis gene mutations — congenital absence of the vas deferens occurs in essentially all men with cystic fibrosis, and it also occurs in men with milder CFTR mutations who have no lung disease at all (Chapter 2.8).
Which means a man presenting with obstructive azoospermia and absent vasa should have CFTR testing, and so should his partner — because if she is a carrier, their child could have cystic fibrosis.
Endocrine causes — pituitary problems, high prolactin, thyroid disease.
Lifestyle and environmental, and this is where action is possible:
Smoking — reduces count, motility and morphology, and increases sperm DNA damage.
Alcohol — heavy use reduces testosterone and sperm quality.
Anabolic steroids — as above, and this is a common and often unmentioned cause in young men.
Obesity — reduces testosterone, raises oestrogen through aromatisation in fat (Chapter 12.6), and raises scrotal temperature.
Heat — saunas, hot tubs, prolonged driving, laptops.
Certain drugs — sulfasalazine, some chemotherapy, and finasteride to a modest degree.
Occupational exposures — pesticides, heavy metals, and organic solvents.
And the encouraging point: most of that list is modifiable, and the effects are measurable within one 3-month cycle.
The declining sperm count question
A meta-analysis published in 2017, updated in 2022, reported that sperm concentrations in Western countries declined by around 50 to 60 percent between 1973 and 2011, with the decline continuing and possibly accelerating.
The findings are taken seriously and they are contested. Criticisms include changes in counting methods over time, selection of the studies included, and variation in the populations sampled.
Proposed causes include obesity, sedentary behaviour, endocrine-disrupting chemicals, heat exposure, and rising paternal age.
The honest position: the trend appears real, its magnitude is uncertain, and its cause is not established. It is worth taking seriously and it does not mean any individual man should be alarmed, because the population average says nothing about one person's fertility.
Vasectomy
The most effective form of male contraception, and among the most effective of any method.
The vas deferens is divided on each side, through a small scrotal incision or by the "no-scalpel" technique using a puncture. Local anaesthetic, 15 to 30 minutes, no hospital stay.
And there is a delay that is critical and frequently mishandled.
Sperm remain in the ducts beyond the point of division for weeks to months. Contraception must be continued until a semen sample confirms azoospermia, usually at 12 to 16 weeks and after at least 20 ejaculations.
Pregnancies after vasectomy occur almost entirely because this was not done, and it is the single most important instruction given.
Failure rate after confirmed clearance is around 1 in 2,000 — lower than female sterilisation.
What it does not affect: testosterone, libido, erection, or ejaculate volume — since sperm are under 5 percent of it (Chapter 15.1). The experience of ejaculation is unchanged.
Reversal is possible and should not be relied on. Success in restoring sperm to the semen is 70 to 90 percent if performed within a few years; pregnancy rates are considerably lower, around 30 to 55 percent, and both decline with the time since the vasectomy — partly because of anti-sperm antibodies (Chapter 15.1).
So vasectomy is counselled as permanent, and men who are uncertain are offered sperm banking or advised to wait.
The concern about prostate cancer risk, raised by some earlier studies, has been examined in very large cohorts and no meaningful association has been found.
What the next page fixes
Chapter 15.3 covers female reproductive anatomy in the same detail — the external and internal structures, the uterus, the tubes, the ovaries, and the pelvic floor — before Chapter 15.4 takes on the cycle.