Puberty, Menstrual Cycle, and Menopause

• Puberty


  The series of events in which a child matures into a young adult, encompassing neuroendocrine and physiologic changes resulting in the ability to ovulate and menstruate
• Puberty sequence


  1. Accelerated growth

  2. Breast development (thelarche)

  3. Development of pubic and axillary hair (pubarche)

  4. Onset of menstruation (menarche)
• Adrenarche


  Occurs between ages 6-8 when the adrenal gland begins regeneration of the zona reticularis, leading to increased production of androgens
• Gonadarche


  Begins around age 8, with increased pulsatile GnRH secretion from the hypothalamus, leading to pulsatile secretion of LH and FSH from the anterior pituitary
• Accelerated growth


  • Growth spurt characterized by acceleration in growth rate around age 9-10, with peak growth velocity around age 12 of about 9 cm per year, due to direct effect of sex steroids on epiphyseal growth and increased pituitary growth hormone secretion
• Thelarche


  Development of breast buds, usually around age 10, in response to increased circulating estrogen
• Pubarche


  Onset of growth of pubic hair, usually around age 11, often accompanied by growth of axillary hair, likely secondary to increased circulating androgens
• Menarche


  Average age of onset of menstruation is between 12-13, or 2.5 years after breast bud development, as gonadal estrogen production increases enough to stimulate endometrial proliferation
• The adolescent menstrual cycle is usually irregular for the first 1-2 years after menarche, reflecting anovulatory cycles
• Menarche is often delayed in gymnasts, distance runners, and ballet dancers, possibly due to insufficient body fat or exercise/stress inhibiting ovulation
• Precocious puberty


  Pubarche or thelarche before 7 years of age in Caucasian girls and before 6 years of age in African American girls
• Delayed puberty


  Absent or incomplete breast development by age 12 years
• Menstrual cycle


  Involves the hypothalamus, pituitary, ovaries, and uterus, divided into follicular and luteal phases, and proliferative and secretory phases
• Follicular phase


  1. FSH stimulates growth of 5-15 primordial ovarian follicles, with one becoming the dominant follicle that produces estrogen

  2. Estrogen enhances follicular maturation and increases FSH/LH receptors
• Ovulation


  Surge in estrogen triggers LH surge, which resumes meiosis in the oocyte and induces progesterone/prostaglandin production to rupture the follicular wall and release the mature ovum
• Luteal phase


  1. Granulosa and theca interna cells form the corpus luteum, which synthesizes estrogen and progesterone to prepare the endometrium for implantation

  2. If fertilization occurs, hCG maintains the corpus luteum; if not, the corpus luteum degenerates and progesterone levels fall, leading to menstruation
• Menstruation


  Withdrawal of estrogen and progesterone causes the endometrium to slough, initiating the menstrual phase
• Perimenopause


  The menopausal transition, beginning 2-8 years before menopause, characterized by irregular ovulatory cycles
• Menstrual cycle


  1. Endometrium undergoes cyclical changes

  2. Follicular phase - endometrium in proliferative phase, growing in response to estrogen

  3. Luteal phase - endometrium enters secretory phase, prepared to support implantation

  4. If ovum not fertilized, corpus luteum degenerates, progesterone levels fall, endometrium sloughs, menstrual phase begins

  5. Follicular phase starts again as FSH levels rise
• Perimenopause


  • Transition from normal ovulatory cycles to menopause, can begin 2-8 years prior to menopause
  • Characterized by irregular menstrual cycles and symptoms associated with menopause like hot flashes, night sweats, mood swings
  • Inhibin B secretion falls, FSH rises, progesterone levels low
• Menopause

  • Defined by 12 months of amenorrhea after final menstrual period, in absence of other causes
  • Characterized by complete or near complete ovarian follicular depletion and absence of ovarian estrogen secretion
• Average age at menopause in US is 51 years
• Factors associated with early menopause

  • Cigarette smoking
  • Short menstrual cycles
  • Nulliparity
  • Type 1 diabetes
  • Family history of early menopause
• Primary ovarian insufficiency (PMOI)

  Onset of spontaneous menopause before age 40
• Physiologic and hormonal changes during menopause

  • Decrease in estrogen
  • Increase in FSH
  • Hot flashes
  • Night sweats
  • Mood swings
  • Vaginal dryness
• 40-80% of women have mild symptoms during perimenopause, 50% experience increased frequency and intensity of symptoms during menopause
• For most women, symptoms may last during first 1-2 years of menopause before gradually decreasing and stopping
• A quarter of women have hot flashes and/or night sweats that extend beyond first 5 years of menopause
• Etiology of menopause


  • Menstrual irregularity as number of oocytes capable of responding to FSH and LH decreases and anovulation becomes more frequent
  • LH and FSH levels gradually rise due to diminished estrogen production
  • Fall in estradiol levels leads to hot flashes, mood changes, insomnia, depression, osteoporosis, vaginal atrophy
• Diagnosis of menopause


  • Usually made by history and physical exam, confirmed by FSH level >40 IU/L
  • Patients present between ages 48-52 with amenorrhea, vasomotor instability, sweats, mood changes, depression, dyspareunia, dysuria
  • Symptoms generally disappear within first 1-2 years, but a substantial proportion remain symptomatic beyond first 5 years
• Physical exam findings in menopause

  • Decrease in breast size and change in texture
  • Vaginal, urethral, and cervical atrophy consistent with decreased estrogen levels
• During perimenopause, FSH level may be increased or decreased
• Long-term consequences of estrogen decrease in menopause

  • Increased risk of coronary artery disease due to loss of estrogen's protective effects on lipid profile and vascular endothelium
  • Accelerated bone resorption leading to osteopenia and osteoporosis
• • 15% of women older than 50 will be diagnosed with osteoporosis, 50% with osteopenia
  • Women can lose 20% of original bone density in first 5-7 years after menopause
• Hormone replacement therapy (HRT)


  • Use of combination estrogen and progesterone to treat menopausal symptoms in women with uterus
  • Progesterone used to decrease risk of endometrial hyperplasia and cancer from unopposed estrogen exposure
• Estrogen replacement therapy (ERT)


  • Use of estrogen only to treat menopausal symptoms in women who have undergone hysterectomy
  • No risk of endometrial hyperplasia or cancer from unopposed estrogen
• Menopausal symptoms


  Due to decreased estrogen levels
• Estrogen component on HRT


  Supplies the patient with an exogenous source of estrogen and thereby treats the symptoms of menopause
• Unopposed estrogen exposure


  Can result in endometrial hyperplasia and/or endometrial cancer
• Progestins


  Used to decrease the risk of endometrial hyperplasia and cancer when estrogens are being used to treat menopausal symptoms in women who still have their uterus in situ