GYN 5

• Physical changes during puberty

  • Breast, pubic and axillary hair growth, growth in height, and menstruation. Most of the changes occur gradually but only the menarche can be dated. There is a lot of variations in the timing of the events. The most common order is beginning of the growth spurt → breast budding (thelarche) → pubic and axillary hair growth (adrenarche) → peak growth in height → menstruation (menarche). All these changes are usually completed between the age of 10 years and 16 years.
• Monomers

  Smaller units from which larger molecules are made
• Polymers


  Molecules made from a large number of monomers joined together in a chain
• Synthetic polymers

  • nylon, polyethylene, polyester, Teflon, epoxy
• Enzymes


  • They increase the rate of chemical reactions without themselves being consumed or permanently altered by the reaction. They increase reaction rates without altering the chemical equilibrium between reactants and products.
• As temperature increases


  The rate of reaction increases
• Controlling factors for onset of puberty

  Genetic, nutrition, body weight, psychologic state, social and cultural background, and exposure to light
• Hypothalamo-pituitary-gonadal axis


  GnRH pulses from hypothalamus results in pulsatile gonadotropin secretion (first during the night then by the day time). GnRH → FSH, LH → Estradiol

  
• Thyroid gland


  Plays an active role in the hypothalamo-pituitary gonadal axis
• Adrenal glands (adrenarche)


  Increase their activity of sex steroid synthesis [androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS)] from about 7 years of age. Increased sebum formation, pubic and axillary hair, and change in voice are primarily due to adrenal androgen production.
• Gonadarche

  Increased amplitude and frequency of GnRH → ↑ secretion of FSH and LH → ovarian follicular development → ↑ estrogen. Gonadal estrogen is responsible for the development of uterus, vagina, vulva, and also the breasts.
• Leptin


  A peptide secreted in the adipose tissue. It is involved in pubertal changes and menarche. Leptin is important for feedback involving GnRH and LH pulsatility. Leptin plays a major link between body composition (body fat proportion), H-P-O axis and thus the menstrual cyclicity.
• Kisspeptin


  A hypothalamic hormone that stimulates the release of GnRH. Kisspeptin is thought to initiate puberty.
• Menarche

  The onset of first menstruation in life. It may occur anywhere between 10 and 16 years, the peak time being 13 years. There is endometrial proliferation due to ovarian estrogen but when the level drops temporarily, the endometrium sheds and bleeding is visible. It denotes an intact hypothalamic pituitary-ovarian axis, functioning ovaries, presence of responsive endometrium to the endogenous ovarian steroids and the presence of a patent uterovaginal canal. The first period is usually anovular. The ovulation may be irregular for a variable period following menarche and may take about 2 years for regular ovulation to occur. The menses may be irregular to start with.

  
• Growth during puberty


  Mainly due to hormones - growth hormone, estrogen, and insulin-like growth factor-1 (IGF-1). The bone or skeletal age is determined by X-ray of hand or knee.
• Changes in genital organs

  Ovaries change their shape, the elongated shape becomes bulky and oval. The uterine body and the cervix ratio changes from 1:2 at birth to 1:1 at menarche and then to 2:1. The vaginal epithelium becomes stratified with many layers rich in glycogen, Doderlein's bacilli appear, and the pH becomes acidic. The vulva and breasts also undergo changes.
• Tanner staging

  Breast and pubic hair development at puberty are divided into five stages.
• Types of precocious puberty

  Isosexual - features due to excess production of estrogen. Heterosexual - features due to excess production of androgen.
• Causes of precocious puberty

  • Constitutional, Intracranial lesions, McCune-Albright syndrome, Premature thelarche, Premature pubarche, Premature menarche, Ovarian, Adrenal, Liver, Iatrogenic
• Diagnosis of true precocious puberty

  • Accelerated growth, skeletal maturation, and epiphyseal closure. Pubertal changes occur in orderly sequence. Tanner staging. No cause detected in majority (90%).

  
• Investigations for precocious puberty


  Serum hCG, FSH, LH, prolactin, thyroid profile, serum estradiol, testosterone, 17-OH progesterone, DHEA. USG, CT or MRI of abdomen, pelvis, brain. Bone age X-ray. GnRH stimulation test.

  
• Premature thelarche


  Isolated development of breast tissue before age 8, without other features of precocious puberty.
• Premature pubarche


  Isolated development of axillary and/or pubic hair prior to age 8 without other signs of precocious puberty.
• Premature menarche


  Isolated event of cyclic vaginal bleeding without any other signs of secondary sexual development.
• Investigations must be carried out to rule out any pathology in the CNS, ovary, and adrenal. Periodic evaluation at 6 monthly intervals is required even if no cause is detected.

  
• Treatment of precocious puberty

  Depends on the cause and speed of progress. Exogenous estrogen therapy may be used.
• Examination under anesthesia or sonography is helpful to detect ovarian or adrenal tumor
• USG, CT or MRI scan is required to detect ovarian or adrenal tumor
• Estimations of serum 17-α-hydroxyprogesterone, DHEA-S and serum testosterone

  Done in suspected cases of adrenal pathology—hyperplasia or tumor
• If nothing abnormal is detected, then the diagnosis of idiopathic pubarche is made

  
• Premature menarche


  The other causes of vaginal bleeding, such as foreign body or injury has to be excluded. If the bleeding is cyclic, the diagnosis is confirmed

  
• Investigations must be carried out to rule out any pathology in the CNS, ovary, and adrenal

  
• Even in cases when no cause can be detected, periodic evaluation at 6 monthly intervals is to be made to detect any life-threatening pathology at the earliest
• Treatment


  1. Exogenous estrogen therapy or its inadvertent intake should be stopped

  2. Cortisone therapy for adrenal hyperplasia

  3. Surgery to remove the adrenal or ovarian tumor

  4. Intracranial tumor requires neurosurgery or radiotherapy

  5. Primary hypothyroidism needs thyroid replacement therapy
• Goals for constitutional or idiopathic precocious puberty

  • To reduce gonadotropin secretions
  • To suppress gonadal steroidogenesis or counteract the peripheral action of sex steroids
  • To decrease the growth rate to normal and slowing the skeletal maturation
  • To protect the girl from sex abuse
  • Assessment of the speed of maturation process
• GnRH agonist therapy


  • Arrests the pubertal precocity and growth velocity significantly
  • Suppresses the premature activation of hypothalamopituitary axis due to down regulation and thereby diminished estrogen secretion
  • Suppresses FSH, LH secretion, reverses the ovarian cycle, establishes amenorrhea, causes regression of breast, pubic hair changes, and other secondary sexual characteristics
• GnRH agonist therapy is the drug of choice in cases with GnRH dependent precocious puberty
• GnRH agonist therapy should be started as soon as the diagnosis is established

  
• GnRH agonist therapy should be continued till the median age of puberty to allow development of maximum adult height
• Medroxyprogesterone acetate


  Can suppress menstruation and breast development but cannot change the skeletal growth rate