Menstrual Cycle and Menopause Flashcards
Hypothalamic-Pituitary-Ovarian Axis
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Hypothalamus
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Gonadotropin Releasing Hormone (GnRH)
- Pulsatile secretion
- Hypothalamic arcuate nucleus → hypothalamic-pituitary portal vascular system
- T½ of 2-4 mins
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Ovarian function requires pulsatile secretion of GnRH in a specific pattern
- Changes throughout the cycle
- Ranges from 60 min to 4 hours
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Gonadotropin Releasing Hormone (GnRH)
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Anterior Pituitary
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Gonadotropins
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Follicle Stimulating Hormone (FSH) & Luteinizing Hormone (LH)
- Glycoprotein hormones
- Pulsatile secretion
- Magnitude and rate secretion determined by ovarian steroid hormone levels
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Follicle Stimulating Hormone (FSH) & Luteinizing Hormone (LH)
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Gonadotropins
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Ovary
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Ovarian Sex Steroid Hormones
- Estrogen and Progesterone
- Also Inhibit A and Inhibit B
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Ovarian Sex Steroid Hormones
Two Cell Theory of Estrogen Production
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Theca cells ⇒ produce androgens
- Responsive to LH
- Androgens enter granulosa cells by diffusion and converted to estrogen
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Granulosa cells ⇒ produce estrone and estradiol
- Responsive to FSH
Menstrual Cycle
Characteristics
- Average age of menarche = 12.4 yrs
- Average age of menopause = 51.4
- Average duration of cycles = 28 days w/ range of 21-35
- Cycle length longer than 35 days = oligomenorrhea
- Cycle length shorter than 21 days = polymenorrhea
- Average blood loss = 20-60 mL (greater than 80 mL is abnormal)
Menstrual Cycle
Ovarian Phases
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Follicular Phase
- All hormones ↓ ⇒ no neg. feedback on FSH
- ↑ FSH ⇒ granulosa cells ⇒ cuboidal, make estradiol, LH receptors
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↑ [Estradiol]
- Mixed action on pituitary gland ⇒ ↓ FSH / ↑ LH
- Several follicles begin to mature
- Dominant follicle emerges (most granulosa cells and FSH receptors, highest estradiol production)
- LH binds theca cells ⇒ prep for production of androgens and progesterone
- Dominant follicle secretes inc. amounts of estradiol (peaks ~ 24 hrs prior to ovulation)
- Feedback on pituitary switches from ⊖ to ⊕ ⇒ ↑↑↑ LH production
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LH surge: cycle day 11-13
- Last for 48 hrs w/ ovulation occurring 36 hrs after the surge
- Non-dominant follicles ⇒ ↑ androgens
- Granulosa and theca cells ⇒ progesterone ⇒ slows follicular phase
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Ovulation
- Process in which the oocyte is released from the follicle
- Occurs 36 hrs after LH surge
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LH surge causes:
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Meiosis of primary follicle resumes ⇒ completion of Metaphase I ⇒ 1st polar body released
- Oocyte arrests in metaphase II until fertilization
- Synthesis of proteolytic enzymes and prostaglandins ⇒ aid in follicular rupture
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Meiosis of primary follicle resumes ⇒ completion of Metaphase I ⇒ 1st polar body released
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Release of the oocyte from the follicle
- ⊗ Genes for follicular phase
- ⊕ Genes for ovulation and luteinization
- Mittelschmerz = brief discomfort noticed by some @ time of ovulation
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Luteal Phase
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Following release of the oocyte, follicle becomes a corpus luteum ⇒ progesterone and inhibin ⇒ ends ovulation
- Granulosa cells → granulosa-lutein cells / theca cells → theca lutein cells
- Estradiol ⇒ ↑ # of LH receptors on granulosa and theca cells
- LH surge ⇒ granulosa cells and theca cells switch from estrogen to progesterone
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Progesterone production begins ~ 24 hrs before ovulation
- Peaks at 3-4 days after ovulation
- Maintained for 11 days after ovulation
- If implantation does not occur, then levels rapidly decrease
- Progesterone ⇒ ⊗ FSH and LH from ant. pituitary
- Inhibin A ⇒ ⊗ FSH
- Estradiol levels drop after LH surge, but then slowly begin to rise again throughout the luteal phase
- Lifespan of corpus luteum is 13-14 days if no conception occurs
- ↓ Estrogen and progesterone ⇒ ↑ FSH ⇒ reinitiate cycle
- Success of this phase dependent on follicular development and proper FSH production
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Following release of the oocyte, follicle becomes a corpus luteum ⇒ progesterone and inhibin ⇒ ends ovulation
Ovarian Menstrual Changes
Uterine Menstrual Changes
- Ovarian follicular phase ⇒ uterine proliferative phase
- Prepares for implantation
- Ovulation ⇒ takes several days for uterus to respond
- Ovarian luteal phase ⇒ uterine secretory phase
- Process for zygote survival
- No pregnancy ⇒ menstruation
Menstrual Cycle
Other Effects
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Endocervix
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Estrogens ⇒ clear, thin, watery mucus
- Max mucus production @ ovulation
- Mucus facilitates sperm capture, storage, and transport
- Ovulation and progesterone ⇒ ↓ mucus production
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Estrogens ⇒ clear, thin, watery mucus
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Breast
- Progesterone in luteal phase ⇒ tenderness and fullness
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Vagina
- Estrogen ⇒ promotes growth of vaginal epithelium & maturation of superficial epithelial cells
- Progesterone ⇒ ↓ vaginal secretions
Hormonal Contraception
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Oral preparations:
- Estrogen + progesterone
- Progesterone only
- Transdermal, injectable, implantable, transmucosal
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Progesterone component provides contraceptive effect
- ⊗ LH secretion ⇒ ⊗ ovulation
- Thickening of endocervical mucus
- ∆ Fallopian tube peristalsis ⇒ ⊗ sperm movement and fertilization
GnRH Agonist
- ⊗ Pituitary gland⇒ ↓LH and FSH
- Initially ⊕ GnRH release ⇒ receptor saturation ⇒ receptor desensitization and down-regulation
- Treatment for endometriosis, uterine fibroids, precocious puberty
- Side effects: hot flushes, night sweats, vaginal dryness, osteopenia
Menopause
Epidemiology
Natural age of menopause is ~ 51 years
In the US, currently 60 million perimenopausal and postmenopausal women
Menopause-related
Disorders
- Major diseases affecting women begin to occur 10 years after menopause
- Cancer, cardiovascular disease, cognitive decline, arthritis, dementia, depression
- Cardiovascular disease = leading cause of death in postmenopausal women
Postmenopausal Woman
Management
Institute prevention strategies @ onset of menopause:
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Sx control and comprehensive issues of quality-of-life
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Vasomotor sx: hot flashes and night sweats
- Affect the overall wellbeing of women, on average persist for 7.4 years
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Vasomotor sx: hot flashes and night sweats
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Promotion of bone health and prevention of osteoporosis
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↓ [Estrogen] ⇒ ↑ bone resorption
- 35% of white postmenopausal women have osteoporosis
- Lifetime fracture risk of 40%
- DEXA scan
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↓ [Estrogen] ⇒ ↑ bone resorption
- Cardiovascular health, combating obesity and metabolic concerns ⇒ education and lifestyle modification
- Prevention and surveillance of cancer ⇒ focus on breast, uterine, and colon
- Prevention of cognitive decline ⇒ lifestyle management and mental stimulation exercises
DEXA scan
(Dual Energy X-Ray Absorptiometry)
- Assessment of bone mass @ hip and spine
- T score ⇒ comparison to peak bone mass of normative group
- Z score ⇒ comparison to age expected bone mass of normative group
- Osteoporosis = T-score more negative than -2.5
Hormone Replacement Therapy
Indications
- Vasomotor sx: hot flashes, night sweats
- Vulvovaginal sx: dryness, painful intercourse
- Prevention of osteoporosis in women at risk
Women’s Health Initiative
Large study w/ a focus on hormonal treatment of menopausal sx
Initial results: ↑ risk of breast CA, CAD, and decline in cognition
Upon further analysis: no sign. ↑ in CAD and actually ↓ coronary events in younger women; no ↑ breast CA risk; reduction in overall mortality; improved verbal memory in women < 60 y/o
Hormone Replacement Therapy
Risks
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Hypertension
- ± Slight ↑ in BP
- Essential HTN is not a contraindication
- Monitor for changes
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Strokes
- Rare occurrence of ischemic strokes
- Highly related to co-morbidities (esp. HTN and obesity)
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Thrombosis
- Related to oral estrogen dose related
- Generally occurs within 1st year of use (underlying thrombophilia)
Alternatives to Hormonal Therapy
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Selective Serotonin Reuptake Inhibitors (SSRI)
- Paroxetine is the only FDA approved medication (other than hormones) for tx of menopausal sx
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
- Gabapentin: generally used if a pt does not respond to SSRI/SNRI
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Clonidine: centrally acting antihypertensive
- Need to use caution in normotensive women
- Soy isoflavones and Black Cohosh: natural remedies, no Rx needed
Hormone Replacement Therapy
Summary
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Disease prevalence inc. substantially ~ 10 yrs after menopause
- Opportunity to institute prevention strategies @ onset of menopause w/ HRT
- Women’s Health Initiative Study was largely misinterpreted
- HRT is efficacious for menopausal sx and prevention of osteoporosis
- HRT in younger women decreases mortality
- Several alternatives for vasomotor sx and preventing osteoporosis
- In younger, healthy women the benefits outweigh the risks
Amenorrhea
Definitions
Amenorrhea: absence of bleeding for at least 3 cycles or at least 6 months in those w/ irregular cycles
Oligomenorrhea: cycles of bleeding w/ intervals longer than 35 days
Polymenorrhea: bleeding that occurs at intervals less than 21 days