Week 12 Reproductive

Breast Cancer Risk Factors

• Most breast cancers develop from mammary duct epithelium or lobular glands.
• Less common types include mucinous, tubular, medullary, papillary, and angiosarcoma.
• Tissue biopsies are tested for hormone receptors (estrogen, progesterone) and the HER2 protein.
• Tumor staging is crucial for prognosis, assessing size, lymph node involvement, and metastasis.
• The upper quadrant is the most frequent location for breast cancer.
• Significant risk factors include increased estrogen exposure (early menses, late menopause), nulliparity, obesity, and PCOS.

Normal Menstrual Cycle

• Menarche marks the first menstrual period; menopause is defined as 12 months of no menses.
• Perimenopause involves months to years of cycle irregularities before cessation.
• Average menstrual cycle lasts 28-35 days; "normal" cycles range between 24-38 days.
• Regular cycles have a variation in length of ≤ 7-9 days.
• Ovarian cycle consists of two phases:
  • Follicular Phase: Occurs from menstruation onset to LH surge, lasting 14-21 days.
  • Luteal Phase: Follows ovulation; hormones support potential pregnancy.

Menopause

• Anti-Müllerian hormone (AMH) decreases and serves as a marker for ovarian reserve, dropping five years before the last period.
• Inhibin B decreases, leading to increased FSH levels around age 35.
• During menopause, LH and FSH levels rise due to reduced inhibin B.
• Testosterone production shifts from ovaries to adrenal glands, with a 25% decline in levels.

Hypothalamic-Pituitary-Ovarian (HPO) Axis

• Regulates female reproduction and menstrual cycle through hormonal communication between the hypothalamus, pituitary gland, and ovaries.
• Involves positive and negative feedback loops for hormones like GnRH, LH, FSH, estrogen, and progesterone.
• The main goal is to coordinate ovulation.

Puberty and Expected Changes

• Puberty spans from the onset of secondary sexual characteristics to full sexual maturity, occurring between ages 8-13 for girls and 8-12 for boys.
• An increase in GnRH secretion from the hypothalamus triggers hormonal changes.
• LH and FSH stimulate steroid production in testes and ovaries, leading to secondary sexual traits.
• Adrenarche results from androgens secreted by the adrenal zona reticularis, functioning separately from the HPO axis.

Clinical Features of Precocious Puberty

• Secondary sex characteristics develop early, with varied patterns:
  • Girls: Thelarche → Pubarche → Menarche.
  • Boys: Testes growth → Scrotum pigmentation → Pubarche.
• In cases of precocious puberty, evaluation of girls under 6 with any secondary characteristic is essential.
• Types include:
  • Gonadotropin Dependent: Early activation of HPO axis, often idiopathic.
  • Gonadotropin Independent: Caused by excess sex steroids; may follow birth control exposure.

Delayed Puberty

• Characterized by inactive HPO axis or ovarian insufficiency, presenting in conditions like Turner syndrome.
• Hypergonadotropic hypogonadism suggests ovarian failure.
• Conditions can include metabolic issues like hypothyroidism or Kallman syndrome, warranting tests for FSH, LH, estradiol, and prolactin.

Tanner Stages

• Tanner 1: Prepubertal stage; only villus hair and elevation of nipple with no breast development.
• Tanner 2: Initial signs of puberty occur between ages 8-11.5, presenting sparse pubic hair and palpable breast buds.

Menstrual Cycle

• Lasts approximately 28 days, with the luteal phase spanning 14 days from LH surge to menses.
• Endometrial Cycle Phases:
  • Desquamation: Shedding of the endometrial lining during menses.
  • Proliferative Phase: Development of endometrial lining with straight, tubular glands.
  • Secretory Phase: Maturation of spiral arteries and endometrial glands for potential pregnancy.

Hormonal Regulation

• Menstrual cycle regulated by the hypothalamic-pituitary-ovarian axis.
• Hypothalamus: Secretes gonadotropin-releasing hormone (GnRH) in a pulsatile manner influenced by biological rhythms and stress.
• Anterior Pituitary: Responds to GnRH by releasing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that stimulate ovarian functions.
• FSH Functions:
  • Stimulates follicular development and egg maturation.
  • Promotes estradiol production from granulosa cells.
• LH Functions:
  • Triggers ovulation via surge mid-cycle.
  • Stimulates theca cells to produce testosterone, converted to estradiol in granulosa cells.

Ovarian Hormones

• Estrogens (Estradiol):
  • Secreted by ovarian follicles in response to FSH.
  • Stimulates endometrial growth and follicle sensitivity to FSH.
  • Inhibits further secretion of FSH, LH, and GnRH during most of the cycle.
  • Positive feedback mid-cycle increases FSH and LH to trigger ovulation.
• Progestins (Progesterone):
  • Secreted by corpus luteum post-ovulation.
  • Prepares endometrium for implantation by stabilizing and thickening the lining.
  • Withdrawal triggers menstrual bleeding.

Pregnancy Hormones

• β-hCG: Major analyte for pregnancy detection produced by the embryo, essential for maintaining pregnancy.
• hCG: Produced by the placenta, increases during the first trimester, linked to nausea.
• Human Placental Lactogen (hPL): Supports fetal nourishment and mammary gland development.
• Estrogen and Progesterone: Regulate pregnancy-related changes, support fetal organ development, and may lead to side effects like nausea and mood swings.
• Oxytocin and Relaxin: Facilitate labor, bonding, and physiological adaptations.

Menopause

• Anti-Müllerian Hormone (AMH): Declines and serves as a marker of ovarian reserve, decreases prior to menarche.
• Inhibin B: Decreases around age 35, impacts FSH secretion levels.
• LH and FSH: Increase due to loss of inhibin B inhibition, reflecting ovarian insufficiency.
• Testosterone: Production shifts from ovaries to adrenal glands, decreases due to adrenal cortex hypoplasia.

Precocious Puberty

• Identification of potential underlying causes involves a detailed history: CNS infections, exposure to endocrine disruptors, family history.
• Early sexual characteristics with specific sequences in girls and boys:
  • Girls: Breast development (thelarche) → Pubic hair (pubarche) → Menarche.
  • Boys: Testicular growth → Scrotal pigmentation → Pubic hair.
• Distinguishing patterns of pubertal progression:
  • Rapid growth and osseous maturation (common in girls).
  • Slow maturation with preserved growth (typical in older girls).
  • Transient central precocious puberty (rarest).

Types of Precocious Puberty

• Gonadotropin Dependent: Early activation of the HPO axis; primarily idiopathic; associated with CNS lesions.
• Gonadotropin Independent: Excess sex steroid secretion from ovaries, often due to autonomously functioning cysts or tumors.
• McCune-Albright syndrome presents with café au lait spots and various endocrine effects.

Delayed Puberty

• May indicate inactive hypothalamic-pituitary-ovarian axis or ovarian insufficiency.
• Can signal metabolic problems, hypothalamic tumors, or Kallmann syndrome.
• Assessment includes evaluating FSH, Estradiol, LH, and Prolactin levels.

Tanner Stages for Female Puberty

• Stage 1 (Prepubertal): Villus hair, only elevation of papillae.
• Stage 2 (8-11.5 years): Sparse pubic hair and noticeable breast buds; thelarche begins.