Delayed puberty

Chapters:

Watch video only

Introduction0:00–0:17

Puberty is the time in an individual’s life when they physically become sexually mature and able to have children. Generally speaking, it’s considered delayed if puberty hasn’t started for a female by age 13 and for a male by age 14.The hypothalamic (HYpo-tha-lamb-ic)-pituitary-gonadal (Go-nad-al) axis is a system of hormonal signaling between the hypothalamus, pituitary gland, and gonads, the gonads are either the testes or the ovaries, and this will control sexual development and reproduction.

Physiology0:17–2:49

Gonadotropin (Go-nad-ah-tro-pin) -releasing hormone is released into the hypophyseal (high-poth-ah-see-al) portal system, which is a network of capillaries connecting the hypothalamus to the hypophysis (high-pof-o-sis), or pituitary.
When gonadotropin(Go-nad-ah-tro-pin) -releasing hormone reach the pituitary gland, it stimulates cells in the anterior pituitary, called gonadotrophs (Go-nad-a-trofs), to release gonadotropin hormones: luteinizing hormone and follicle-stimulating hormone which then enter the blood.
These gonadotropin hormones then stimulate the gonads to produce sex specific hormones. These are estrogen and progesterone in females and testosterone is the major sex specific hormone in males.
Early on in male development, testosterone helps the external sex organs to differentiate into male genitals and causes the testes to descend from the abdomen into the scrotal sac.
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 as well, it 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 characteristic that we see during puberty.
Primary sex characteristics refers to the genitals, which are the 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.

Tanner scale2:49–4:29

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 pre-pubertal 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 and there’s 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 something called a “mound-on-mound” contour.
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.
Puberty is delayed if progression through the Tanner scale hasn’t begun by the time 95% of an individual’s peers have begun to sexually mature.
Generally, that means puberty has not started by age 13 in females and age 14 in males. Hypogonadism, or lower levels of sex hormones from low gonad activity, is central to a delay in puberty.
As a result, sex characteristics are under-developed. Permanent infertility can occur if puberty never begins or fails to complete and sexual maturity is never reached.

Primary hypogonadism4:29–5:26

There are two main causes of hypogonadism. The first is primary hypogonadism which is caused by dysfunction of the gonads - for example, the gonad’s receptors may not respond to gonadotropin hormones, or the gonads might not have healthy cells that are capable of producing hormone.
Some acquired causes of primary hypogonadism are radiation therapy, chemotherapy, and trauma to the gonads. Some congenital causes of primary hypogonadism are genetic diseases like Klinefelter or Turner syndrome.
Regardless of the cause, the result is a decrease or absence of testosterone in males, or estrogen and progesterone in females, which means there’s no negative feedback on the hypothalamus.
This leads to an overproduction of luteinizing and follicle stimulating hormones so primary hypogonadism is also called hypergonadotropic hypogonadism.The second cause of hypogonadism is secondary hypogonadism, which is also called hypogonadotropic hypogonadism because there are low levels of luteinizing and follicle stimulating hormones.

Secondary hypogonadism5:26–6:27

Secondary hypogonadism can be due to hypothalamus or pituitary gland dysfunction; either from an inability to produce gonadotropin-releasing hormone or luteinizing and follicle stimulating hormones, or suppression from other hormones, like prolactin or thyroid hormone.
Some acquired causes are similar to primary hypogonadism, radiation therapy, chemotherapy, and trauma to the gonads. Other ones include a tumor of the pituitary gland and hypothalamus, and congenital causes include Kallmann syndrome and panhypopituitarism.
And general causes include chronic illness, like cystic fibrosis or celiac disease, excessive exercise, malnutrition or obesity, and stress - all of which affect the way the hypothalamus and pituitary release hormones.

Constitutional delay6:27–7:19

A third category, called constitutional delay, is a temporary delay in puberty which does not typically result in infertility.
Just like in secondary hypogonadism, there’s a lack of gonadotropin-releasing hormone, but the key difference is that it’s not considered pathologic - instead, it’s thought to be a naturally slowed rate of maturation.
The onset of puberty can still occur naturally and puberty can progress normally after onset, it just all happens at a later age.
Typically, there’s a genetic component to constitutional delays and it runs in families.A delay in puberty is usually diagnosed by comparing an individual’s sexual development with the Tanner scale.
Blood tests of hormone levels can give an idea of the type of hypogonadism. And a detailed medical history, including evaluating any underlying medical conditions and family history for constitutional delay can be helpful.
The treatment for a delay in puberty depends on the cause. A constitutional delay can resolve on its own with a natural onset of puberty, and does not typically require medical intervention.

Treatment7:19–7:43

If an underlying medical condition is the cause, hormone therapy is necessary to ensure the onset and normal progression of puberty.
Infertility treatments may also be needed to make reproduction possible. So, to recap: Delayed puberty usually means that it hasn’t started for a female by age 13 and for a male by age 14.

Review7:43–8:11

Though there are different causes which result in different levels of gonadotropin hormones, they all ultimately result in hypogonadism and a deficiency in testosterone or estrogen and progesterone.
In contrast, a constitutional delay is when the onset of puberty might still occur naturally with puberty progressing normally after onset, but it just occurs at a later age.