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6. HDS GI Repro > Menstrual Cycle and Menopause > Flashcards

Menstrual Cycle and Menopause Flashcards

1
Q

Hypothalamic-Pituitary-Ovarian Axis

A
  • Hypothalamus
    • Gonadotropin Releasing Hormone (GnRH)
      • Pulsatile secretion
      • Hypothalamic arcuate nucleus → hypothalamic-pituitary portal vascular system
      • T½ of 2-4 mins
    • Ovarian function requires pulsatile secretion of GnRH in a specific pattern
      • Changes throughout the cycle
      • Ranges from 60 min to 4 hours
  • Anterior Pituitary
    • Gonadotropins
      • Follicle Stimulating Hormone (FSH) & Luteinizing Hormone (LH)
        • Glycoprotein hormones
        • Pulsatile secretion
        • Magnitude and rate secretion determined by ovarian steroid hormone levels
  • Ovary
    • Ovarian Sex Steroid Hormones
      • Estrogen and Progesterone
    • Also Inhibit A and Inhibit B
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2
Q

Two Cell Theory of Estrogen Production

A
  • Theca cells ⇒ produce androgens
    • Responsive to LH
  • Androgens enter granulosa cells by diffusion and converted to estrogen
  • Granulosa cells ⇒ produce estrone and estradiol
    • Responsive to FSH
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3
Q

Menstrual Cycle

Characteristics

A
  • 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)
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4
Q

Menstrual Cycle

Ovarian Phases

A
  • Follicular Phase
    • All hormones ↓ ⇒ no neg. feedback on FSH
    • ↑ FSH ⇒ granulosa cells ⇒ cuboidal, make estradiol, LH receptors
    • ↑ [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
    • 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
  • Ovulation
    • Process in which the oocyte is released from the follicle
    • Occurs 36 hrs after LH surge
    • LH surge causes:
      • 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
    • 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
  • Luteal Phase
    • 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
    • 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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5
Q

Ovarian Menstrual Changes

A
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6
Q

Uterine Menstrual Changes

A
  • 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
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7
Q

Menstrual Cycle

Other Effects

A
  • Endocervix
    • Estrogens ⇒ clear, thin, watery mucus
      • Max mucus production @ ovulation
      • Mucus facilitates sperm capture, storage, and transport
    • Ovulation and progesterone ⇒ ↓ mucus production
  • Breast
    • Progesterone in luteal phase ⇒ tenderness and fullness
  • Vagina
    • Estrogen ⇒ promotes growth of vaginal epithelium & maturation of superficial epithelial cells
    • Progesterone ⇒ ↓ vaginal secretions
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8
Q

Hormonal Contraception

A
  • Oral preparations:
    • Estrogen + progesterone
    • Progesterone only
  • Transdermal, injectable, implantable, transmucosal
  • Progesterone component provides contraceptive effect
    • ⊗ LH secretion ⇒ ⊗ ovulation
    • Thickening of endocervical mucus
    • ∆ Fallopian tube peristalsis ⇒ ⊗ sperm movement and fertilization
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9
Q

GnRH Agonist

A
  • ⊗ 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
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10
Q

Menopause

Epidemiology

A

Natural age of menopause is ~ 51 years

In the US, currently 60 million perimenopausal and postmenopausal women

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11
Q

Menopause-related

Disorders

A
  • 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
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12
Q

Postmenopausal Woman

Management

A

Institute prevention strategies @ onset of menopause:

  • Sx control and comprehensive issues of quality-of-life
    • Vasomotor sx: hot flashes and night sweats
      • Affect the overall wellbeing of women, on average persist for 7.4 years
  • Promotion of bone health and prevention of osteoporosis
    • ↓ [Estrogen] ⇒ ↑ bone resorption
      • 35% of white postmenopausal women have osteoporosis
      • Lifetime fracture risk of 40%
    • DEXA scan
  • 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
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13
Q

DEXA scan

(Dual Energy X-Ray Absorptiometry)

A
  • 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
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14
Q

Hormone Replacement Therapy

Indications

A
  • Vasomotor sx: hot flashes, night sweats
  • Vulvovaginal sx: dryness, painful intercourse
  • Prevention of osteoporosis in women at risk
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15
Q

Women’s Health Initiative

A

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

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16
Q

Hormone Replacement Therapy

Risks

A
  • Hypertension
    • ± Slight ↑ in BP
    • Essential HTN is not a contraindication
    • Monitor for changes
  • Strokes
    • Rare occurrence of ischemic strokes
    • Highly related to co-morbidities (esp. HTN and obesity)
  • Thrombosis
    • Related to oral estrogen dose related
    • Generally occurs within 1st year of use (underlying thrombophilia)
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17
Q

Alternatives to Hormonal Therapy

A
  • 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
  • Clonidine: centrally acting antihypertensive
    • Need to use caution in normotensive women
  • Soy isoflavones and Black Cohosh: natural remedies, no Rx needed
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18
Q

Hormone Replacement Therapy

Summary

A
  • 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
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19
Q

Amenorrhea

Definitions

A

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

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20
Q

Types of Amenorrhea

A
  • Primary
    • No menses by age 13 w/o secondary sexual characteristics
    • No menses by age 15 w/ secondary sexual characteristics
  • Secondary
    • Menstruating female w/o menses for 3-6 months or the duration of 3 typical cycles in a pt w/ oligomenorrhea
21
Q

Amenorrhea

Etiologies

A
  • Pregnancy
  • Hypothalamic pituitary dysfunction
  • Ovarian dysfunction
  • Alteration of outflow tract
22
Q

Pregnancy

A

Most common cause of secondary amenorrhea

Urine hCG (cheap and easy)

23
Q

Hypothalamic Pituitary Dysfunction

A

Low FSH, low LH

Hypogonadotropic Hypogonadism

  • Functional ⇒ low FSH, low LH, nl prolactin
    • Weight loss (extreme)
    • Obesity
    • Excessive exercise (lean body mass)
  • Drug Induced ⇒ low FSH, low LH, nl prolactin
    • Marijuana
    • Psychiatric drugs: antidepressants
  • Neoplastic
    • Prolactin secreting pituitary adenoma ⇒ low FSH, low LH, high prolactin
    • Craniopharyngioma
    • Hypothalamic hamartoma
    • Radiation
  • Other
    • Chronic medical illness: ESRD
    • Inherited: Kallman Syndrome, Idiopathic hypogonadotropic hypogonadism
24
Q

Ovarian Dysfunction

A

High FSH, high LH

Hypergonadotropic Hypogonadism

  • Chromosomal Abnormality
    • Gonadal dysgenesis
    • Abnormal Karyotype
      • Turner Syndrome 45X
    • Normal Karyotype
      • Single gene disorders
        • Mutations in CYP17 gene: leads to ↓ estrogen
  • Gonadotropin-resistant ovarian syndrome:
    • Mutation of LH and/or FSH receptors
  • Premature natural menopause: idiopathic
  • Autoimmune ovarian failure: polyglandular failure (thyroid & adrenal)
25
Q

Alteration of Outflow Tract

A

Primary

Labial agglutination, imperforate hymen, transverse septum, cervical stenosis, Mullerian agenesis

Secondary

Asherman Syndrome: synechia (scar tissue) following trauma to the endometrium

26
Q

Amenorrhea

Evaluation

A
  • History
  • Physical Exam
  • Laboratory/Imaging
  • Progesterone Challenge Test
    • Determine adequate estrogen, competent endometrium and patent outflow tract
    • Give 10mg Provera daily for 10 days
    • Induce a withdrawal bleed a few days after completing the oral course
    • ⊕ Bleeding ⇒ anovulation or oligo-ovulation
    • ⊖ Bleeding ⇒ hypo-estrogenic or anatomic
27
Q

Amenorrhea

Treatment

A
  • Hyperprolactinemia
    • Amenorrhea w/ galactorrhea
      • Treat w/ cabergoline or bromocriptine
        • Dopamine agonists
      • Check for hypothyroidism (5%)
        • Low thyroxine levels ⇒ ↑ TRH & ↓ dopamine ⇒ ↑ prolactin
    • If pregnancy is desired:
      • Clomiphene citrate, pulsatile GnRH, aromatase inhibitors
  • Oligo/anovulation
    • OCP to regulate cycle
    • Clomiphene citrate if pregnancy desired
  • Abnormal Genital Tract
    • Surgery
    • Hymenotomy
    • Removal of septum
    • Mullerian agenesis cannot be repaired
  • Hypothalamic Pituitary Dysfunction
    • Pulsatile GnRH or human menopausal gonadotropins
28
Q

Abnormal Uterine Bleeding

Definitions

A
  • Menorrhagia: prolonged or excessive bleeding at regular intervals; > 7 days or > 80 mL
  • Metrorrhagia: irregular intervals of bleeding
  • Menometrorrhagia: prolonged bleeding at irregular intervals
29
Q

Menstruation Pathophysiology

A
  • Endometrium consists of 2 distinct layers
    • Basalis layer
      • Direct contact w/ myometrium
      • Serves as the source of regeneration for functionalis layer
      • Less responsive to hormones
    • Functionalis layer
      • Lies above basalis layer
      • Lines endometrial cavity
      • Responds to cyclic hormonal changes
      • Layer that is sloughed during menstruation
  • Blood Supply
    • Uterine and ovarian arteries ⇒ uterus
    • Uterine aa → arcuate aa → radial aa → basal and spiral aa
      • Basal aa ⇒ basalis layer
      • Spiral aa ⇒ functionalis layer
    • Spiral aa → arterioles
      • Become increasingly coiled and demonstrate stasis of blood flow prior to menses
      • Give rise to a network of capillaries which vasodilate and bleed
      • Subsequent vasoconstriction ⇒ ischemia and necrosis
      • Process ultimately leads to sloughing of the endometrial lining w/ menstruation
30
Q

Abnormal Uterine Bleeding

Etiologies

A
  • Complications of Pregnancy
  • Structural Causes (PALM)
  • Nonstructural Causes (COEIN)
31
Q

Abnormal Uterine Bleeding

Complications of Pregnancy

A

First trimester spontaneous abortion (miscarriage)

  • Threatened abortion (threatened miscarriage) ⇒ Os closed
  • Inevitable abortion ⇒ Os open
  • Incomplete abortion ⇒ Os open, intrauterine tissue
  • Complete abortion ⇒ Os closed, no intrauterine tissue
  • Missed abortion
  • Septic abortion
  • Ectopic pregnancy
  • Hydatidiform mole, choriocarcinoma (Gestational trophoblastic disease)
32
Q

Abnormal Uterine Bleeding

Structural Causes

A

(PALM)

  • Polyp
  • Adenomyosis
  • Leiomyoma
    • Submucosal Leiomyoma
    • Other Leiomyoma
  • Malignancy and hyperplasia
33
Q

Abnormal Uterine Bleeding

Nonstructural Causes

A

(COEIN)

  • Coagulopathy
  • Ovulatory dysfunction
  • Endometrial
  • Iatrogenic
  • Not yet classified
34
Q

Abnormal Uterine Bleeding

History

A
  • Menstrual hx: age at menarche, cycle length, number of days of flow, character of bleeding, and amount
  • Weight change
  • Stress (physical, mental/ chronic, acute)
  • Medical hx: chronic systemic illnesses, unusual bleeding, prolonged bleeding or easy bruising, thyroid disease, etc.
  • Surgical hx: especially gynecologic
  • Medications
  • Family hx
  • Social hx: including abuse
35
Q

Abnormal Uterine Bleeding

Physical Exam

A
  • Skin: Hirsutism, acne, pigmentation/striae
  • Weight, height: obesity, leanness
  • Thyroid: mass, diffuse enlargement
  • Breast: development, galactorrhea
  • Abdominal: mass
  • Pelvic: abnormal development, clitoromegaly, mass
  • Rectal: presence of hemorrhoids
36
Q

Abnormal Uterine Bleeding

Diagnostic Evaluation

A
  • Laboratory tests
    • Always:
      • Pregnancy test (β-hCG level)
      • CBC w/ platelet count (iron studies if needed)
    • If indicated:
      • TSH
      • Prolactin
      • FSH, LH
      • Testosterone
      • DHEAS
      • Progesterone
      • Coagulation Profile
        • Esp. in adolescents (at least 5% of hospitalized pts w/ bleeding dyscrasia and/or leukemia)
      • PT; PTT; Factor VIII; von Willebrand’s Factor antigen
      • Chlamydia trachomatis
  • Imaging
    • Pelvic US
    • Sonohysterogram
    • Hysteroscopy
    • MRI
  • Tissue sampling methods
    • Endometrial Biopsy (office vs OR)
37
Q

Abnormal Uterine Bleeding

Age-Based Common DDx

A
  • 13-18 y/o
    • Anovulation (immature HPO)
    • OCP use
    • Pregnancy
    • Pelvic infection
    • Coagulopathies
  • 19-39 y/o
    • Pregnancy
    • Structural lesions
    • Anovulatory cycles
    • OCP use
    • Endometrial hyperplasia
  • 40 y/o – menopause
    • Anovulatory bleeding (declining ovarian function)
    • Endometrial hyperplasia
    • Endometrial atrophy
    • Structural lesions
38
Q

Anovulatory Bleeding

Treatment Overview

A

Primary goal in tx is to ensure regular shedding of endometrium

Progesterone for minimum of 10 days per month

Oral contraceptive pills (OCP)

39
Q

Anovulatory Bleeding

Medical Management

A

Acute episodes of bleeding

  • Control the current episode
    • High dose estrogen/progestin therapy
    • OCP cascade (monophasic regimen)
      • Severe blood loss but pt hemodynamically stable
      • Does not cause rapid endometrial proliferation
      • Not as effective as combine equine estrogen (CEE)
    • IV estrogen (combine equine estrogen [CEE])
      • Rapid cellular proliferation of denuded and raw surfaces of endometrium
      • ↑ Platelet aggregation
  • Prevent future episodes
    • OCP/IUD
    • Progestins (progestogens which act like progesterone)
      • Stop endometrial growth
      • Allows stabilization of endometrium ⇒ organized sloughing
      • ↑ Arachidonic acid ⇒ ↑ PGF2a (potent vasoconstrictor)
      • Not for acute situations
    • NSAIDS
      • Prostaglandin inhibitors
      • Reduction of blood loss up to 50%
    • GnRH analogs
      • Binds GnRH receptor ⇒ gradual downregulation ⇒ ↓ release of GnRH
      • Induces medical menopause by suppressing HPO axis
      • Temporizing measure because long term may lead to bone loss (osteopenia and/or osteoporosis)
    • Blood transfusion(s) and Iron supplementation when indicated
40
Q

Estrogen Risks

A
  • Estrogen
    • ↑ Risk of thrombosis
      • Contraindications:
        • Estrogen dependent tumor
        • Hx of DVT
        • Some rheumatologic diseases
      • In these cases, progestins should be used
  • OCPs
    • Relative contraindications: cardiovascular disease, HTN, DM
    • Contraindicated: women > 35y/o who smoke, hx of thromboembolism
41
Q

Anovulatory Bleeding

Surgical Management

A

1° tx for organic or structural cause (e.g. leiomyoma, polyp, cancer)

When medical tx fails or is contraindicated

  • Dilation and curettage
    • Can be diagnostic and therapeutic
    • Enhanced by use of hysteroscopy
  • Endometrial Resection or Ablation
    • Endometrium removed or resected w/ electrocautery or heated saline inside an intrauterine balloon, microwave
    • ± Hormonal pretreatment ⇒ thin endometrial lining
    • Alternative to hysterectomy
    • Low risk procedure in general but complications can be significant
    • Fluid overload, uterine perforation w/ subsequent damage to major organs
    • Not for women who want to maintain fertility
  • Uterine Artery Embolization
    • Effective and less invasive option for women w/ leiomyomata
    • Performed by Interventional Radiology
    • Small microspheres injected into uterine aa ⇒ ⊗ blood flow to uterus
    • Causes necrosis of myomas
    • With time reduces the amount of blood loss w/ menses
    • Successful in approximately 90% of women
    • Not for women who want to maintain fertility
  • Hysterectomy
    • Performed by laparotomy, laparoscopy or robot
    • Definitive tx
    • Performed once childbearing is complete
42
Q

Polycystic Ovarian Syndrome

Overview

A
  • Most common cause of androgen excess and hirsutism
  • Etiology is unknown
  • Symptoms: Oligomenorrhea/amenorrhea, Acne, Hirsutism, Infertility
43
Q

Polycystic Ovarian Syndrome

Diagnosis

A
  • Primarily defined by androgen excess
  • Rotterdam Criteria (must have 2)
    • Oligoovulation or anovulation (irregular menstrual cycles)
    • Biochemical or clinical evidence of hyperandrogenism
    • Polycystic appearing ovaries on ultrasound
  • Need to rule out:
    • Congenital adrenal hyperplasia
    • Cushing’s Syndrome
    • Hyperprolactinemia
44
Q

Polycystic Ovarian Syndrome

Pathophysiology

A
  • Anovulation in PCOS ⇒ constant, non-cyclic estrogen production
  • Stimulates growth and development of endometrium
  • Endometrium outgrows blood supply
  • Sloughs at irregular intervals and in unpredictable amounts
  • Ultimately results in irregular bleeding
45
Q

Polycystic Ovarian Syndrome

Associated Conditions

A
  • Obesity is linked to PCOS in many pts
  • Metabolic Syndrome
    • 40% of pts w/ PCOS have impaired glucose tolerance
    • 8% have Type 2 DM
  • Lipid abnormalities
  • HTN
46
Q

Polycystic Ovarian Syndrome

Labs

A
  • ↑ LH:FSH ratio
  • ↑ Estrone compared to estradiol
  • ↑ Testosterone
  • ↑ Androstenedione
47
Q

Polycystic Ovarian Syndrome

Complications

A
  • Endometrial hyperplasia or cancer
  • DM
  • HLD
  • Metabolic syndrome
  • Cardiovascular disease
48
Q

Polycystic Ovarian Syndrome

Treatment

A
  • Most common tx is OCPs
    • ⊗ Pituitary LH ⇒ ↓ androstenedione and testosterone
      • Acne clear
      • New hair growth is prevented
  • If conception is desired:
    • Weight reduction
    • Clomiphene citrate
    • Metformin

6. HDS GI Repro (30 decks)

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