Puberty and Menopause

Question 1

Define puberty.

Answer 1

A phase of development between childhood and complete, functional maturation of the reproductive glands and external genitalia(adulthood)

Question 2

Name the 2 physiological events in puberty.

Answer 2

1. Gonadarche is the activation of reproductive glands by the pituitary hormones: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
2. Adrenarche is the increase in production of androgens by the adrenal cortex

Question 2

What are the components of puberty?

Answer 2

Thelarche, Pubarche, Menarche

Question 3

Define thelarche.

Answer 3

Onset of breast development, which is primarily due to the action of estradiol from the ovaries

Question 3

Define pubarche.

Answer 3

Onset of pubic hair growth, primarily due to the effects of androgens from the adrenal gland. The term is also applied to the first appearance of axillary hair, apocrine body odor, and acne.

Question 3

Define menarche.

Answer 3

Onset of menstrual bleeding.

Question 4

Describe the physiology of puberty.

Answer 4

Unknown initial trigger → ↑ activators and/or ↓ inhibitors of GnRH secretion → pulsatile GnRH secretion→ ↑ FSH and ↑ LH secreted by the gonadotroph cells of the anterior pituitary gland → stimulation of the Leydig cells and Sertoli cells in the testicles, and the theca and granulosa cells in the ovary.

FSH stimulates the growth of ovarian follicles and together with LH, stimulates production of estradiol by the ovaries

Estradiol stimulates breast development and growth of the skeleton, leading to pubertal growth acceleration

Pituitary secretion of FSH and LH, and secretion of estradiol by ovarian follicles leads to ovulation and menstrual cycles

Question 5

What is the sequence of pubertal maturation in girls?

Answer 5

1. Adrenarche
2. Gonadarche
3. Thelarche (age of onset 8–11 years)
4. Growth spurt (age of onset 11.5–16.5 years)
5. Pubarche (mean age of onset 12 years)
6. Menarche (age of onset 10–16 years, mean age: 13 years)

Question 6

What is the sequence of pubertal maturation in boys?

Answer 6

1. Adrenarche
2. Gonadarche (age of onset 9–14 years)
3. Pubarche (mean age of onset 13.5 years)
4. Growth spurt (mean age of onset 13.5 years)
5. Androgenic hair growth

Question 7

What is the first visible sign of puberty in males and females?

Answer 7

Testicular enlargement and breast development

Question 8

What are the determinants of pubertal timing?

Answer 8

• General health (nutritional state, bodyweight)
• Genetics
• Social environment (e.g., family stress)

Question 9

Describe the Tanner’s staging for pubic hair and breast development.

Answer 9

See slide 17 of handout

Question 10

Name 5 issues that arise with puberty.

Answer 10

• Anaemia associated with menarche
• Myopia: due to axial growth of the eye
• Acne vulgaris
• Psychological changes
• STIs
• Unplanned pregnancy
• Eating disorders
• Depression, suicide
• Motor vehicle accidents

Question 11

Define precocious puberty.

Answer 11

Onset of pubertal development at an age that is 2 to 2.5 standard deviations (SD) earlier than population norms

Usually before the age of eight years in girls and nine years in boys

Question 12

What are the 3 types of precocious puberty?

Answer 12

1. Central precocious puberty
2. Peripheral precocity
3. Benign or nonprogressive pubertal variants

Question 13

Define central precocious puberty.

Answer 13

Precocious puberty with elevated GnRH levels - Early activation of the hypothalamic-pituitary-ovarian axis leads to pulsatile GnRH secretion, increased gonadotropin and increased gonadal steroid hormone levels

Question 14

Give 2 causes of precocious puberty.

Answer 14

Idiopathic (most common cause)

CNS lesions
Intracranial tumours (e.g., hamartoma, glioma, craniopharyngioma)
Trauma
Infections (e.g., encephalitis, meningitis)
Hydrocephalus

Radiation

Question 15

How is central precocious puberty diagnosed?

Answer 15

Lab tests
1. Serum LH and FSH: increased
2. GnRH stimulation test (gold standard): evaluates the reactivity of the hypothalamic-pituitary-axis to GnRH stimulation
Gonadotropin (LH and FSH) levels increase after intravenous administration of GnRH.
3. Serum testosterone/oestradiol: increased

Imagining
1. X-ray of the nondominant hand and wrist: allows comparison between skeletal maturation and chronological age
Assess and confirm accelerated bone
2. MRI/CT of the brain with contrast: when ↑ LH is confirmed

Question 16

How is central precocious puberty managed?

Answer 16

• GnRH agonist e.g., leuprolide, buserelin, goserelin
  >Close monitoring of therapy
  >Follow-up is recommended every 4–6 months to assess progression
• Manage underlying cause

Question 17

Define peripheral precocious puberty.

Answer 17

Precocious puberty without elevated GnRH levels - due to ↑ peripheral synthesis of or exogenous exposure to sex hormones

Question 18

How is peripheral precocious puberty treated?

Answer 18

Precocious puberty caused by excessive hormonal production from a tumor in the body: surgical removal

Precocious puberty caused by congenital adrenal hyperplasia: cortisol replacement

Ovarian cysts: no intervention is necessary (spontaneous resolution is common)

Hypothyroidism is treated with thyroid hormone replacement

For those with exogenous exposure, halting the estrogen source, such as hormonal pills or creams, is sufficient.

Question 18

Give 3 causes of peripheral precocious puberty.

Answer 18

1. Increased Androgen production
   Congenital adrenal hyperplasia
   Virilising ovarian and adrenocortical tumours (e.g., Sertoli-Leydig cell tumour, Leydig-cell tumour)
2. Increased Oestrogen production
   McCune-Albright syndrome
   HCG-secreting germ cell tumours (e.g., dysgerminomas)
3. Increased β-hCG production
   Dysgerminoma
   Malignant embryonal cell carcinoma
   Choriocarcinoma
4. Primary hypothyroidism
5. Exogenous steroid use e.g. medications, creams

Question 18

How is peripheral precocious puberty diagnosed?

Answer 18

Lab tests

Serum basal FSH and LH: decreased
GnRH stimulation test
No increase in LH levels after GnRH administration.

Serum testosterone/oestradiol levels: increased (depending on the tumour)

TSH, T3 hormone: suspicion of hypothyroidism

Serum DHEA-S and 17-hydroxyprogesterone: in cases of hyperandrogenism

Corticotropin stimulation test: suspicion of congenital adrenal hyperplasia or an adrenal tumour

Imaging

X-ray of the nondominant hand and wrist: accelerated bone growth

Ultrasound of the ovaries, testicles, and abdomen (cases of increased ovarian and/or uterine volume than expected for age, diagnostic uncertainty

Question 19

Define delayed puberty.

Answer 19

Absent or incomplete development of secondary sex characteristics by the age of 14 years in boys or 13 years in girls

Question 20

Give 3 pathological causes of delayed puberty.

Answer 20

1. Hypergonadotropic hypogonadism 2. Hypogonadotropic hypogonadism 3. Malnutrition (e.g., anorexia nervosa) 4. Chronic diseases (e.g., inflammatory bowel disease, hypothyroidism, cystic fibrosis)

Question 20

Define hypergonadotropic hypogonadism.

Answer 20

A condition characterized by the gonads (testes in males and ovaries in females) being unresponsive to stimulation by gonadotropins (LH and FSH)

Question 20

What are the 2 categories of hypergonadotropic hypogonadism?

Answer 20

1. Primary gonadal insufficiency – Dysfunction of the gonads e.g., Klinefelter syndrome, Turner syndrome, androgen insensitivity syndrome 2. Secondary gonadal insufficiency – Gonadal injury e.g., chemotherapy, pelvic irradiation, infections, trauma/surgery, autoimmune disease

Question 21

Define hypogonadotropic hypogonadism.

Answer 21

Insufficient production of gonadotropin hormones from the hypothalamus or pituitary gland leading to inadequate sex hormone production by the ovaries or testes

Question 21

What is Kallmann syndrome, Prader-Willi syndrome and Gaucher disease

Answer 21

Kallman syndrome - A rare genetic condition characterized by anosmia (an inability to smell) and decreased production of GnRH from the hypothalamus, leading to delayed or absent puberty Prader Willi syndrome - A genetic syndrome caused by microdeletion of the paternal gene copy at 15q11-q13. The condition is characterized by muscular hypotonia during infancy, genital hypoplasia, short stature, and hyperphagia, which often results in morbid obesity. Gaucher disease - An autosomal recessive disease caused by a deficiency in β-glucocerebrosidase that leads to intracellular accumulation of glucocerebroside in the brain, liver, spleen, and bone marrow. Causes hepatosplenomegaly, neurodegeneration, osteoporosis, and aseptic necrosis of the femur. The most common lysosomal lipid storage disease

Question 22

How is delayed puberty managed?

Answer 22

Treatment of the underlying disease Hormonal therapy Testosterone: used in boys to achieve secondary sex characteristics (e.g., virilization, growth spurt) Boys with constitutional growth delay usually respond well after one or two courses of testosterone therapy. If little or no response is seen, isolated GnRH deficiency should be suspected in boys over the age of 18 years. Estradiol: used in girls with primary gonadal insufficiency (e.g., Turner syndrome) Initially: low-dose estradiol that is gradually increased After 2 years: Add cyclic progestin therapy to induce menstruation.

Question 23

Define induced, premature and early menopause.

Answer 23

Induced menopause - the permanent loss of ovarian function as a result of medical interventions e.g. ovarian ablation due to chemotherapy, radiation, bilateral oophorectomy. Clinical features may be more pronounced because of the rapid drop in hormone levels and vasomotor symptoms are more severe and frequent in surgical menopause. Premature menopause - the permanent cessation of ovarian function and menses before the age of 40 years. Caused by induced menopause. Early menopause - the occurrence of physiological menopause between 40 and 45 years of age with no other identified cause.

Question 24

Define the following terms: a) Pre-menopause b) Perimenopause c) Menopause d) Post-menopause

Answer 24

a) Pre-menopause- begins with menarche and ends with the onset of perimenopause b) Perimenopause– the length of time from the first occurrence of irregular menstruation cycles to 12 months after the final menstrual period c) Menopause– the date of an individual's final menstrual period d) Post-menopause– the time after the FMP; the first 12 months are called early post-menopause

Question 25

Which factors influence menopause? (4)

Answer 25

- Environmental – smoking hastens the age of menopause by approximately 2 years - Genetics – familial factors Chemotherapy, pelvic radiation, and ovarian surgery may also lead to earlier menopause - Diet - Exercise - Socioeconomic status

Question 26

Give 7 clinical features of menopause

Answer 26

1. Menstrual abnormalities Irregular menses that gradually decrease in frequency until complete amenorrhea Typically develop shorter cycles though longer cycles are possible 2. Vasomotor symptoms of menopause Increased sweating Hot flashes Heat intolerance Impaired sleep e.g. insomnia and/or night sweats 3. Neuropsychiatric symptoms Anxiety/irritability Mood swings or depression Poor concentration, poor memory 4. Sexual dysfunction Decreased libido Vaginal dryness Dyspareunia 5. Other symptoms Changes to hair distribution - Hirsutism (due to a relative increase in androgens) - Female pattern hair loss - Thinning pubic hair 6. Weight gain 7. Patients may also present with complications of menopause (e.g., osteoporosis, cardiovascular disease).

Question 27

What is the genitourinary syndrome of menopause?

Answer 27

Vulvovaginal atrophy leading to: - Vaginal dryness - Dyspareunia - Decreasing labial fat pad - Pruritus - Pelvic organ prolapse - Spotting or bleeding after sex - Elevated vaginal pH Lower urinary tract atrophy leading to: - Dysuria - Urinary frequency and/or urgency - Urinary incontinence - Recurrent urinary tract infections

Question 28

What does the mnemonic HAVOC stand for

Answer 28

Hot flashes/Heat intolerance, Atrophy of Vagina, Osteoporosis, Coronary artery disease, Sleep impairment

Question 29

How is menopause managed?

Answer 29

- Hormone Replacement Therapy - Promotion of a Healthy Lifestyle

Question 30

Give 5 side effects of HRT.

Answer 30

- Breast soreness - Mood changes - Bloating - Vaginal bleeding - Thromboembolic events - Oestrogen-sensitive cancer (e.g., endometrial cancer, breast cancer) - Headache - Gastrointestinal upset (e.g., nausea, bloating), - Weight gain, retained fluid