Precocious puberty

Puberty is the time in an individual’s life when they physically become sexually mature and able to have children. Precocious refers to puberty occurring at an earlier age than the average age among an individual’s peers. Generally, puberty is considered precocious if it begins before the age of 8 in females and the age of 9 in males.

The hypothalamic-pituitary-gonadal axis is a system of hormone signaling between the hypothalamus, pituitary gland, and gonads, either the testes or ovaries, to control sexual development and reproduction. Gonadotropin-releasing hormone is released by the hypothalamus into the hypophyseal portal system, which is a network of capillaries connecting the hypothalamus to the hypophysis, or pituitary. When gonadotropin-releasing hormone reach the pituitary gland, it stimulates cells in the anterior pituitary, called gonadotrophs, to release gonadotropin hormones: luteinizing hormone and follicle-stimulating hormone into the blood. These gonadotropin hormones then stimulate the gonads to produce specific steroids, sex hormones.

Beginning at puberty, the Leydig cells of the testes respond to the luteinizing hormone by converting more cholesterol into testosterone. In addition, the Sertoli cells of the testes respond to follicle-stimulating hormone by producing more sperm. The major sex specific hormones in women are estrogen and progesterone, and they are produced by the ovarian follicles that are scattered on the ovaries. Each ovarian follicle is made up of a ring of granulosa and theca cells surrounding a primary oocyte at its core. Beginning at puberty, theca cells respond to luteinizing hormone by producing androstenedione, an androgen. Then, the granulosa cells respond to follicle stimulating hormone by converting the androstenedione into estrogen and progesterone.

Waves of estrogen and progesterone regulate monthly changes to the ovary stroma to promote egg maturation and ovulation, and changes to the uterine wall lining as part of the menstrual cycle. The increased production of sex hormones drives the development of primary and secondary sex characteristics observed during puberty. Primary sex characteristics refers to the genitals, organs directly involved in sexual reproduction. Secondary sex characteristics refers to any sex-specific physical characteristic that is not directly involved or necessary in sexual reproduction, like pubic hair and breasts, in females.

The Tanner scale, or Tanner stages, is a predictable set of steps that males and females go through as they develop primary and secondary sex characteristics and become sexually mature. The Tanner scale centers on two, independent criteria: the appearance of pubic hair in both sexes; and the increase in testicular volume and penile size and length in males, and breast development in females. There are five stages: In stage 1, the prepubertal stage, no pubic hair is present in either sex. Males have a small penis and testes. Females have a flat-chest. In stage 2, pubic hair appears; there is a measurable enlargement of the testes; and breast buds appear. In stage 3, pubic hair becomes coarser; the penis begins to enlarge in both size and length; and breast mounds form. In stage 4, pubic hair begins to cover the pubic area; the penis begins to widen; and breast enlargement continues to form a “mound-on-mound” contour of the breast. In stage 5, pubic hair extends to the inner thigh; the penis and testes have enlarged to adult size; and the breast takes on an adult contour.

Precocious puberty is when a child starts progressing through the Tanner scale before 95% of other children that age. Generally, that means puberty has started before the age of 8 in females and 9 in males. Precocious puberty is usually due to a central or peripheral problem. Central precocious puberty, or gonadotropin-dependent precocious puberty, results from early maturation of the hypothalamic-pituitary-gonadal axis. When that happens, it causes an early release of luteinizing hormone and follicle-stimulating hormone which in turn causes an increase in sex hormones. Ultimately, early maturation of the hypothalamic-pituitary-gonadal axis could be due to a dysfunctional hypothalamus or pituitary gland. One cause could be a tumor that’s releasing gonadotropin releasing hormones or human chorionic gonadotropin, a placental hormone that’s similar to luteinizing hormone. Another cause is an infection or cyst or radiation damage to the brain that impairs the negative feedback system in the hypothalamic-pituitary-gonadal axis. But most of the time, there’s no identifiable pathology and it’s simply called idiopathic precocious puberty. Idiopathic precocious puberty is considered a normal variation in the age at which puberty begins, and it’s influenced by factors like when a parent began puberty as well as an individual's weight. The other category - peripheral precocious puberty, or gonadotropin-independent precocious puberty, is the result of the abnormal overproduction of sex hormones by the testes or ovaries. This could be caused by an ovarian or testicular cyst or tumor, genetic conditions, like McCune-Albright syndrome, dysfunction of other glands, like the thyroid or adrenal gland; or exogenous sex hormones from medications and creams.