PHARM 8: Menopause Flashcards
3 main players in the menopause progression?
AMH
Inhibin
FSH
- Cycles > 60 Days apart
- Normal FSH/Intermitently Elevated (Compensatory mechanisms fails)
- FSH High
Late Menopausal Transition (-1)
- > 7 Day difference in cycle length
- Variable FSH
- Ovarian Reserve Low
Early menopausal Transition (-2)
- Cycles Slightly Irregular
- Normal FSH/Intermittently Elevated
- Ovarian Reserve Low
Late Reproductive Stage (-3)
Progression of Menopause Stages
Cycle Length?
FSH?
Ovarian Reserve?
Late Reproductive Stage (-3)
- Cycles Slightly Irregular
- Normal FSH/Intermittently Elevated
- Ovarian Reserve Low
Early menopausal Transition (-2)
- > 7 Day difference in cycle length
- Variable FSH
- Ovarian Reserve Low
Late Menopausal Transition (-1)
- Cycles > 60 Days apart
- Normal FSH/Intermitently Elevated (Compensatory mechanisms fails)
- FSH High
Early Menopause (+1)
- Menses have ended
- FSH High
- Ovarian Reserve undetectable
CNS changes in menopausal transition?
During menopausal transition Hypothalamic-pituitary axis (HPA) appears to lose sensitivity to both positive and negative feedback by estrogen
Estrogen withdrawal as well as aging causes hypertrophy of a subpopulation of neurons in the infundibular nucleus expressing estrogen receptor
Earliest Signs and Symptoms of Menopause?
Prediction of Onset?
Earliest signs: Irregular bleeding patterns, changes in frequency and bleeding duration
Symptoms most prevalent and severe during first 1 to 2 years after final menstrual period
Earlier symptoms development in transition = longer duration bothersome symptoms (sometimes more than a decades)
AMH prediction: In women age 35 to 44 years old – every ↓ AMH by 0.1 ng/mL below 2ng/mL, a 14% higher risk early menopause before 45
Vasomotor symptoms (VMS) of Menopause?
Risks?
Hot flashes: Due to rapid rise in body temperature with accompanying vasodilation
Hormone therapy (HT) most effective
Severe and prolonged VMS associated with↑CV risk burden due to loss of endothelial function
Genitourinary Symptom of Menopause (GSM)?
Therapy?
Changes to lower genital tract due to estrogen deprivation:
- Atrophy of the vulva and vagina, vagina dryness, vaginal narrowing, uterine prolapse and urinary incontinence
- ↓ Oestrogen => reduced blood flow to vagina => reduced
secretions, increased pH, decrease surface epithelium
Oestrogen replacement alleviate most of GSM except for urinary incontinence
Bone symptoms of menopause?
- Oestrogen is a potent antiresorptive agent at bone level
- Hypoestrogenism of menopause = increase rate bone resorption
- ↓ GI Ca2+ absorption => promotes osteoclast-mediated bone resorption via upregulated PTH
- Peak bone density achieved around age 30 and progressively declines at 0.7% per year:
- Rate bone loss increase dramatically a year before final menstrual period and persist up to 3 years (as high as 5% per year) then slows again to approach the rate of loss prior to menopause
Diagnosis of Menopause?
Cessation of menses for at least 12 months
DO NOT MEASURE Sex steroids, gonadotropins, inhibin B, or AMH
Persistent FSH elevation in women < age 40 provides a tentative diagnosis
First-line Menopause Treatment?
Estrogen Therapy (ET) for those without a uterus
Estrogen + Progestogen Therapy (EPT) for those with
a uterus
Benefits of Transdermal Estradiol preparation?
- Less thrombotic – suitable for women with higher thrombotic risk (BMI >30)
- Suitable for borderline hypertriglyceridemia, risk of gallstones, poor adherence to oral medication or if taking other oral medications.
- Less nausea
Non-hormonal Treatment of Vasomotor symptoms (VMS) of Menopause: For Women unable to take an estrogen because of risk factors or unable to tolerate HT.
________________ and ______________________: effective for treating VMS in women unable to take HT
____________:
- Moderately effective for hot flushes
- SE drowsy, unsteadiness, dizzy. Use at night might mitigate SEs
____________
- Antihypertensive
- Reduces hot flushes
- Less effective than SSRI, SNRI or Gabapentin
SSRIs (Paroxetine, Escitalopram) and SNRIs (Venlafaxine): effective for treating VMS in women unable to take HT
Gabapentin:
- Moderately effective for hot flushes
- SE drowsy, unsteadiness, dizzy. Use at night might mitigate SEs
Clonidine
- Antihypertensive
- Reduces hot flushes
- Less effective than SSRI, SNRI or Gabapentin
