Across the lifespan

The HPG axis is unusual among endocrine systems in that it spends most of childhood switched off, briefly reawakens just after birth, then activates fully at puberty and gradually declines in later life. Tracing it from conception to senescence is also a tour of how the body changes across the lifespan.

Fetal life

The story begins around gestational week 6–7, when the SRY gene on the Y chromosome (in a 46,XY embryo) triggers the bipotential gonad to differentiate into a testis. The fetal testis begins producing testosterone by week 8, driving development of the Wolffian ducts (which become the epididymis, vas deferens, and seminal vesicles). DHT — a more potent androgen made from testosterone by 5α-reductase — drives formation of the external male genitalia. Sertoli cells produce anti-Müllerian hormone (AMH), which suppresses the female-pattern Müllerian duct system.

In 46,XX embryos, the absence of SRY allows the bipotential gonad to develop into an ovary, the Müllerian system to persist (forming the fallopian tubes, uterus, and upper vagina), and the Wolffian system to regress.

During the third trimester, a fetal HPG-axis burst drives the descent of the testes into the scrotum and the final stretch of penile growth. Failure here results in cryptorchidism (undescended testes) or micropenis at birth — early markers of severe congenital HPG-axis dysfunction.

Minipuberty (birth through about six months)

Shortly after birth, removal of placental sex steroids unmasks the infant hypothalamus, which briefly resumes pulsatile GnRH release. LH and FSH rise nearly to pubertal levels, and testosterone surges to mid-pubertal levels for a few months before falling back. This transient activation is called minipuberty.

Minipuberty is functionally important. It:

• Completes testicular descent if not already done.
• Supports normal newborn penile growth.
• Drives proliferation of Sertoli cells in the testis. Sertoli-cell number is set during this window and barely changes afterwards. Adult sperm-production capacity is proportional to Sertoli-cell number, which is why severe congenital hypogonadism that abolishes minipuberty limits adult fertility potential even if treatment is started later.

Minipuberty also provides a diagnostic window: in infants with cryptorchidism or micropenis, measuring LH, FSH, and testosterone in the first months of life can detect congenital hypogonadism early, before the long childhood silence makes the diagnosis harder.

By around six months, central inhibition reasserts itself and the axis goes quiet again.

Childhood — the quiet years

From roughly six months until adrenarche, the HPG axis is held in check by central inhibition. GnRH neurons exist and are functional but are suppressed by inhibitory inputs (GABA, opioids, and others). LH, FSH, and testosterone sit at very low levels. The testes remain small (1–3 mL), penile growth is slow and proportional, and there are no signs of pubertal development.

This quiet period serves real developmental purposes: it lets the brain mature, the body grow without the demands of reproductive maturation, and the various neuroendocrine systems develop in coordination.

Adrenarche (about ages 6–8)

A separate process — adrenarche — begins around ages 6–8, when the adrenal glands start producing increasing amounts of DHEA and DHEA-S. This is independent of the HPG axis — it does not involve GnRH, LH, or FSH, and it can be intact even when the HPG axis is failing.

Adrenarche produces the first visible signs of approaching maturation: faint pubic hair, the beginnings of body odor, occasional mild acne. These are often mistaken for the start of puberty proper but represent a separate adrenal process. Some children experience pronounced adrenarche (“premature adrenarche”) which is generally benign and self-limited.

Pubertal reawakening (about ages 9–14)

The HPG axis reactivates over a period of roughly 1–2 years before any visible external signs appear. The trigger is incompletely understood, but the leading candidate is the kisspeptin / KNDy network (see pulsatility) “releasing the brake” on the GnRH pulse generator. Energy status — particularly leptin from adipose tissue — plays a permissive role, which is why severely underweight children often have delayed puberty.

The earliest hormonal change is the return of pulsatile GnRH release, initially only during sleep. This nocturnal pulsatility drives the first LH pulses of puberty, which are measurable on overnight sampling before any daytime change. Over the next year or two the pulsatility extends into daytime hours and stabilizes at the adult pattern of one pulse every 60–120 minutes.

The visible course of male puberty follows the Tanner stages:

• Stage 2 — the first physical sign of true puberty: testicular enlargement past 4 mL volume, driven by FSH stimulating Sertoli-cell proliferation. Scrotum thins and reddens; sparse, fine pubic hair appears at the base of the penis; the growth rate begins to rise. Testosterone climbs into the low pubertal range.
• Stage 3 — penile lengthening begins, testes grow further, pubic hair coarsens and spreads, the growth spurt accelerates, the voice begins to change subtly, body odor becomes more pronounced, mild acne and transient gynecomastia may appear. Testosterone rises substantially.
• Stage 4 — the growth spurt peaks, penile girth develops, the voice deepens noticeably, axillary hair appears, spermarche (the onset of sperm production) typically occurs, body composition shifts toward more muscle mass. Testosterone approaches adult levels.
• Stage 5 — adult configuration: adult genital size, pubic hair extending to medial thighs, broadening shoulders and chest, facial and body hair filling in over years, final adult height reached as the bones’ growth plates fuse under the influence of estradiol.

Female puberty follows an analogous course, with the breast (B) and pubic-hair (P) staging tracking ovarian and adrenal androgen development, and culminates in menarche, the first menstrual cycle. The whole life stage is treated in more detail under adolescence and puberty.

The endocrine summary

If the hormones are plotted across this timeline the pattern is:

• GnRH pulsatility — absent through childhood, returns first as nocturnal pulses at the start of puberty, extends into daytime, then settles at the adult ~90-minute interval.
• LH — flat through childhood, nocturnal pulses, then a rising daytime presence, finally the adult pulsatile pattern.
• FSH — flat through childhood, rises slightly earlier than LH at the start of puberty, then continues climbing to its adult plateau.
• Testosterone — prepubertal (very low) until Tanner 2, then rises progressively through the stages to the adult range by Tanner 4–5.
• Inhibin B — rises early in puberty as Sertoli cells respond to FSH; reaches adult range by mid-puberty.
• AMH — elevated through childhood, falls during puberty as Sertoli cells mature.
• DHEA / DHEA-S — rises from adrenarche onward, independent of the HPG axis, reaching adult levels by the late teens.
• Estradiol (in males) — rises modestly through puberty from peripheral conversion of testosterone.

Adulthood

The adult axis is a stable oscillator, holding hormones in their adult range and supporting fertility, libido, and the maintenance of secondary sex characteristics. The female axis carries an additional layer: the menstrual cycle, a recurring monthly pattern of follicular growth, the mid-cycle LH surge that triggers ovulation, and corpus-luteum progesterone supporting the second half of the cycle — driven by a positive-feedback exception where sustained high estradiol flips the pituitary from negative to positive feedback for one or two days.

Senescence

The axis’s behavior in later life differs sharply between the sexes.

• In females, menopause is an abrupt event. Around the late 40s to mid-50s, ovarian follicles are exhausted, estradiol and progesterone fall, and the negative feedback on the pituitary disappears — so LH and FSH rise to very high levels. Cycles cease. The accompanying symptoms (vasomotor instability, bone loss, urogenital atrophy) reflect estradiol withdrawal across a wide range of target tissues.
• In males, there is no equivalent abrupt event. Testosterone drifts down gradually from the third decade onward at roughly 1% per year, and a meaningful fraction of older men develop late-onset hypogonadism. The pattern is mixed — partly a slowly failing testis (Leydig cells decline with age), partly a less responsive central drive. Spermatogenesis can continue into old age, though fertility declines.

Senescence of the axis is part of aging more broadly.

Key idea

The axis is a developmental clock as much as an endocrine system: it organizes the body’s transition through fetal sex differentiation, infant minipuberty, the long childhood quiet, the dramatic awakening of puberty, the stable adult steady state, and the gradual or abrupt decline of later life. Many disorders of the axis present at the moment of a transition — most often at puberty — because that is when the demands on the system change.