20. Puberty

Step-fathers and puberty

, girls with step-fathers reach puberty faster (9mo earlier) than those without. Of those undergoing puberty under 12, 18% of girls are from intact homes, 25% are from divorced homes, and 35% have stepfathers. It is thought that perhaps a strange male induces sexual readiness in young females. This is seen in mice, and is called the Vandenbergh effect (even the urine of a strange male can induce readiness).

Tanner stage

A criteria for the timing and sequence of the development of secondary sexual characteristics during puberty. There is a lot of variation, but this criteria allows for abnormalities to be detected. This criteria is based on Europeans so is not reflective of other ethnicities

Hormonal changes during female puberty

In foetal life, there are some rises and falls in hormones, leading to inhibitory cycles developing early on in development. After birth, the plasma levels of gonadotrophins may be in the adult range, rising and falling intermittently for the first two years of life. This is related to the loss of placental hormones They decline and remain very low during childhood, until the initiation of events leading to puberty. At puberty, you get an LH surge every month, with underlying changes in FSH. At menopause, there is an elevation of both FSH and LH.

Oestrogen in puberty

In girls, oestradiol levels rise consistently through the stages of puberty to reach the concentrations seen in mature females. Oestrogen is responsible for secondary sexual changes, growth and development of the breasts and reproductive organs, fat redistribution, and bone maturation. In boys, oestrogen levels are lower than in girls.

The Gonadostat hypothesis

In this hypothesis, there is a progressive maturation of the hypothalamus, changing the feedback action of oestradiol or testosterone on gonadal secretion and also causing changes in the pituitary responsiveness to GnRH. Pre-puberty, the negative feedback regulation of FSH and LH secretion operates at a very low threshold or set point, and therefore is very sensitive to low levels of steroids (just a small amount of the sex steroids is needed to inhibit the hypothalamus and prevent more secretion. At puberty, this set point increases to become less sensitive (more sex steroid is needed to cause inhibition). This leads to rising concentrations of gonadotrophins and sex steroids in the circulation during puberty.

Fat stores and puberty

It is thought that perhaps fat stores are important in the initiation of puberty: when they are adequate, enough leptin can be produced to cause the onset of puberty

Explain Menarche

Menarche occurs at an average age of 12-13 years (95% of girls will experience their first menstruation between 11 and 15. There is a huge amount of variation. However, the first ovulation does not take place until 6-9 months after menarche, because the positive feedback mechanisms of oestrogen have not developed. Regular ovulatory cycles are established 1-2 years after menarche. For the first few years, cycles will be longer due to an inability to ovulate. It takes quite a long time for them to settle down, but you will generally get regular menstrual cycles between 20 and 40.

Define Spermarche

Onset of spermatogenesis, driven by androgens

Define Adrenarche

Adrenal maturation, driven by androgens

Precocious Puberty

Precocious puberty is the appearance of the physical and hormonal signs of puberty before 7yrs in white girls, 6yrs in African-American girls, and 9yrs in boys (used to be 8 years). This is 2 standard deviations below the mean. Some of these individuals falling at the extreme edges may be a part of natural variation, but there may also be something of concern. For example, children with hypothalamic tumours may undergo precocious puberty.

Age of onset of puberty, how this had changed, and the issues with this

Puberty used to occur around 17 or 18yo, but this age has dropped significantly to 12-13yo. The age at which girls first menstruate shows a considerable range within the population, but there has been a clear trend towards earlier menarche in girls, and puberty in boys over the last decade, although it now seems to have plateaued at 13 years old. This increased rate of sexual maturation, combined with a slow rate of neural maturation and an increasingly complex social setting have led to some disastrous behaviours such as binge drinking in our adolescents.

Explain Pubarche (Males)

Pubic hair generally appears about 6 months after the beginning of testicular enlargement, but this is purely coincidental as they are controlled by different mechanisms. Axillary hair begins to grow 18 months later, then facial hair later after that.

Define Pubarche

Appearance of pubic hair, driven by androgens

Body shape in boys and girls

Body shape in boys and girls is determined by the differential effects of oestrogen and androgen. Males tend to be more muscular, taller, and aggressive. Females show fat distribution to buttocks and breasts, as well as growth and widening of the pelvis to provide a larger birth canal (triggered by oestrogen). This creates an hourglass figure, which is believed to signal reproductive success. Women generally have a higher body fat percentage. About 22% body fat is required to hold a pregnancy - most athletes are under this! To be most fertile, you must not be too fat nor too thin. Once menopause is reached, a woman's body shape begins to change to more of an apple, male-like shape.

Explain the growth spurt (females and males)

Bone changes correlate with secondary sexual characteristics better than chronological age. This can be important for assessment of precocious puberty. After breast development in girls, and testicular enlargement in boys, we see increased growth acceleration. Growth is stimulated by steroid hormone (oestrogen and androgen), with epiphyseal closure stimulated by oestrogen. If there is something wrong with oestrogen signalling, there will be excessively long arms. In girls, the growth spurt begins ~11-12, and full adult height is reached ~17. In boys, the growth spurt begins at ~13-15, and full adult height is reached ~21.

Define Thelarche

Breast development, driven by oestrogens

Issues with precocious puberty

Children with untreated precocious puberty do not reach full adult height potential (action of oestrogen causes premature epiphyseal closure). Boys will generally grow to less than 1.6m, and girls to less than 1.5m The children will also experience emotional distress.

Define Menarche

First menstruation, driven by oestrogens

Treatment of precocious puberty

GnRH dependent precocious puberty can be treated with GnRH agonists which will temporarily stop puberty, preserving adult height potential. GnRH independent precocious puberty treatment is individualised, and based on the underlying disorder.

Frequency of precocious puberty

GnRH dependent precocious puberty is a rare disorder, affecting 1/5000 to 1/10000 children. There is a female gender preference, with 23 girls to every 1 boy. Some girls diagnosed with precocious puberty may actually be normal girls in the early end of the normal distribution.

What drives puberty?

Hormonal changes drive both the behavioural and physical responses

Explain the process of Thelarche

The first physical sign of secondary sexual maturation occurs at age ~10-11. The breast bud rises on the chest wall following oestradiol secretion by the ovarian follicles. At this stage, primary follicles will develop but none will mature, as there is not enough FSH and LH. In fact, at this stage the ovaries may even look polycystic due to the number of follicles trying to grow. The nipples and areolae enlarge and elevate, followed by formation of a breast mound. Ovulation, with subsequent progesterone secretion, leads to full breast development.

Testicular and penile enlargement

The first signs of secondary sexual development in the male is enlargement of the testicles. Gonadotropin secretion causes Leydig cells to enlarge and secrete testosterone, affecting the seminiferous tubules, giving rise to increased testicular size. Elongation and enlargement of the penis begins within a year of testicular development.

GnRH and LH in puberty

The increase in plasma LH levels is the first neuroendocrine sign of puberty, and is the result of an increase in GnRH release (in frequency, amplitude and baseline). LH is detected rather than GnRH as GnRH is only detectable in the hypophyseal portal vein which is very difficult to access, whereas LH is easily detectable in the blood. Gonadotrophin secretion (both FSH and LH) occurs only at night during sleep in early puberty. From early to mid-puberty, a striking increase in the magnitude and frequency of LH pulses occurs, which reflects a sleep-augmented LH secretion. In late puberty, daytime LH pulses also increase.

Puberty

The physical, emotional, and sexual transition from childhood to adulthood. The transition is gradual, and is punctuated by well-defined events and milestones

The Hypothalamic Maturation Hypothesis

This hypothesis suggests that puberty is driven by a primary change in the hypothalamic output of GnRH. In this hypothesis, puberty onset is suppressed by feedback inhibition on the HPG axis, and a suppression of GnRH release by central neural pathways Puberty onset results from: • Increased stimulation of GnRH neurons • Decreased inhibition of GnRH neurons • Increased production of glial growth factors It is thought that the fat hormone, Leptin, triggers the activation of pulsatile GnRH secretion. The neuropeptides kisspeptin and neurokinin b are also thought to play a role. There is both an increased frequency in GnRH pulses, and an increase in the baseline level of GnRH.

What makes the gonadostat hypothesis not believable?

This is a very old hypothesis, and largely is not believed any more. This is because even in individuals who don't have gonads, we still see the same change in gonadotropin secretions (just don't get puberty because of a lack of sex steroid production). Therefore, something else must be involved.

Explain Spermarche

This is the beginning of spermatogenesis. Spermarche refers to the first ejaculation with sperm present, although in the early days there is not much sperm. As a surrogate marker (as making a young boy ejaculate is frowned upon), sperm in the urine can also be observed. Motile sperm is seen in the urine at ~13-14 years, and the first conscious ejaculation occurs soon after (14+)

Explain Adrenarche

This is the earliest endocrine change. Adrenarche is a progressive increase in the plasma concentration of the adrenal androgens; DHEA, DHEAS and androstenedione. This is distinct from hypothalamic-pituitary-gonad maturation Adrenal maturation is selective, in that glucocorticoid and mineralocorticoid secretion (other adrenal hormones) does not increase at this time. Adrenarche starts around 8 years of age, and continues until 13-15 years. The only clear function of these adrenal androgens appears to be the promotion of pubic and axillary hair growth. This could be an evolutionary thing, related to pubic hair being a sign of sexual maturation or allowing pheromone release. Perhaps it is just a bit out of signal with the rest of puberty?

Delayed puberty

This is the lack of appearance of the physical and hormonal signs in puberty at ~13yrs in females, and ~14yrs in males. It occurs when the gonadotrophin signals from the pituitary are inadequate to produce follicular maturation and subsequent sex steroid hormone secretion.

Why do we think the age of onset of female and male puberty has decreased?

This is thought to be due to reaching the critical weight at an earlier time. In girls, a critical weight must be attained before the activation of the hypothalamo-pituitary-gonadal axis and the growth spurt can occur. According to this view, body weight, a critical metabolic rate, mass related to body weight, or a ratio of fat to lean mass may trigger the changes in hypothalamic feedback. This could potentially be related to Leptin levels. In girls, the mean weight at the beginning of the growth spurt is around 30kg, and menarche is around 47kg. There is however a lot of variation in this. A similar suggestion has been made for a critical weight of 55kg underlying sexual maturation in boys. The idea of the critical weight being required for puberty is supported by the loss of menstrual function seen in sports amenorrhoea and anorexia - signalling that there is not enough body fat to sustain pregnancy and lactation. There is not a lot of evidence for this. There may also be other factors at play.

Explain Pubarche (Females)

This occurs usually within 6 months of the appearance of the breast bud at age ~10-12. Due to exposure of hair follicles on the mons pubis and labia majora to androgens. While breast development usually occurs first, in ~15% of girls, pubic hair will occur first. If pubic hair development occurs more than 6 months prior to breast development, there may be an androgen excess disorder. Axillary (armpit) hair follows approximately 1 year after pubic hair development. Apocrine glands of the mons pubis and axillae enlarge and begin excreting volatile organic acids, leading to an adult body odour.

Kallman Syndrome

characterised by delayed puberty and a lack of sense of smell, due to GnRH deficiency that reflects a primary defecit in the formation of GnRH neurones in the olfactory region in the developing brain

GnRH dependant (central or true) Precocious puberty

• Early activation of the pulsatile GnRH secretion • Most common form of precocious puberty • May be idiopathic (cause unknown) or due to CNS lesions or injury, congenital anomalies, or genetic diseases.

What are the physical changes of puberty?

• Growth of the genitals • Appearance of secondary sex characteristics.

What are the behavioural responses of puberty

• Increase in libido • Erotic fantasies • Sexual behaviour

Causes of Delayed puberty

• Kallman Syndrome • Neurological tumours (primarily in the anterior region of the hypothalamus) • Low body weight, exercise induced amenorrhoea, and stress-induced amenorrhoea.

GnRH independent (peripheral or pseudo-precocious puberty

• Occurs when the gonads operate independantly of the hypothalamic-pituitary unit, for example, through premature sex steroid secretion • Secondary to ovarian cysts or tumours, testicular tumours, or syndromes such as McCune Albright Syndrome.

Testosterone in puberty in boys

Rise in testosterone levels in plasma follow the gonadotropins. In early puberty, testosterone levels in boys rise at night when LH secretion becomes elevated. Later in puberty, levels will rise during the day too.