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GY34 Gynecology
Menopause
Toronto Notes 2019
Menopause Pathophysiology
Degenerating theca cells fail to react to endogenous gonadotropins (FSH, LH)
Less estrogen is produced
Decreased negative feedback on hypothalamic-pituitary-adrenal axis
Increased FSH and LH
Stromal cells continue to produce androgens as a result of increased LH stimulation
Figure 18. Menopause pathophysiology
• Osteoporosis is the single most important health hazard associated with menopause
• Cardiovascular disease is the leading cause of death post-menopause
• Increased risk of breast cancer (RR 1.3) is associated with estrogen+progesterone HRT, but not with estrogen-only HRT
• All women taking HRT should have periodic surveillance and counselling regarding its benefits and risks
Treatment
• goalisforindividualsymptommanagement ■ vasomotor instability
◆ HRT (first line), SSRIs, venlafaxine, gabapentin, propranolol, clonidine
◆ acupuncture ■ vaginal atrophy
◆ local estrogen: cream (Premarin®), vaginal suppository (VagiFem®), ring (Estring®)
◆ lubricants (Replens®)
◆ oral or transdermal hormone replacement therapy (if treatment for systemic symptoms is desired) ◆ intravaginal laser
■ urogenital health
◆ lifestyle changes (weight loss, bladder re-training), local estrogen replacement, surgery
■ osteoporosis
◆ 1,000-1,500 mg calcium OD, 800-1,000 IU vitamin D, weight-bearing exercise, smoking cessation ◆ bisphosphonates (e.g. alendronate)
◆ selective estrogen receptor modifiers (SERMs): raloxifene (Evista®) – mimics estrogen effects on
bone, avoids estrogen-like action on breast and uterine cancer; does not help hot flashes ◆ HRT: second-line treatment (unless for vasomotor instability as well)
■ decreased libido
◆ vaginal lubrication, counselling, androgen replacement (testosterone cream or the oral form
Andriol®)
■ cardiovascular disease
◆ management of cardiovascular risk factors ■ mood and memory
◆ antidepressants (first line), HRT (augments effect)
■ alternative choices (not evidence-based, safety not established)
◆ black cohosh, phytoestrogens, St. John’s wort, gingko biloba, valerian, evening primrose oil, ginseng, Don Quai
Hormone Replacement Therapy
• seeFamilyMedicine,FM40
• primaryindicationistreatmentofmenopausalsymptoms(vasomotorinstability) • keepdoseslow(e.g.0.3mgPremarin®)anddurationoftreatmentshort(<5yr)
HRT Components
• estrogen
• oralortransdermal(e.g.patch,gel)
• transdermalpreferredforwomenoverall,especiallywithhypertriglyceridemiaorimpairedhepatic
function, smokers, and women who suffer from headaches associated with oral HRT
• low-dose(preferreddose:0.3mgPremarin®/25μgEstradot®patch,canincreaseifnecessary)
• progestin
• givenincombinationwithestrogenforwomenwithanintactuterustopreventdevelopmentof
Table 17. Examples of HRT Regimens
endometrial hyperplasia/cancer
HRT Regimen
Unopposed Estrogen
Standard-Dose
Standard-Dose Cyclic
Pulsatile Transdermal
Topical
Estrogen Dose
CEE 0.625 mg PO OD CEE 0.625 mg PO OD
CEE 0.625 mg PO OD
CEE 0.625 mg PO OD
Estroderm®-Estradiol 0.05 mg/d or 0.1 mg/d Estalis®-Estradiol
140 μg/d or 250 μg/d
Estrace® 2-4 g/d x 1-2 wk, 1 g/d maintenance Premarin® 0.5-2 g/d for 21 d then off 7 d for vaginal atrophy, 0.5 g/d for 21 d then off 7 d or twice/wk for dyspareunia
Estragyn® 2-4 g/d
Progestin Dose
None
MPA 2.5 mg PO OD, or micronized progesterone 100 mg PO OD
MPA 5-10 mg PO
days 1-14 only, or micronized progesterone 200 mg PO OD days 1-14 only
MPA low-dose
Estroderm®-MPA 2.5 mg PO OD Estalis®-NEA
50 μg/d
Crinone® 4% or 8% (45 or 90 mg applicator)
Notes
If no intact uterus
Withdrawal bleeding may occur in a spotty, unpredictable manner
Usually abates after 6-8 mo due to endometrial atrophy
Once patient has become amenorrheic on HRT, significant subsequent bleeding episodes require evaluation (endometrial biopsy)
Bleeding occurs monthly after day 14 of progestin (can continue for years)
PMS-like symptoms (breast tenderness, fluid retention, headache, nausea) are more prominent with cyclic HRT
3 d on, 3 d off
Use patch twice weekly
Can use oral progestins (Estroderm®) Combined patches available (Estalis®)
If simultaneously taking oral estrogen tablet, may need to adjust dosing
If intact uterus, also take progesterone
CEE = conjugated equine estrogen (e.g. Premarin®); MPA = medroxyprogesterone acetate (e.g. Provera®); NEA = norethindrone acetate
Consider lower dose regimens, PREMPRO® 0.45/1.5 (Premarin® 0.45 mg and Provera® 1.5 mg); Estrace® (topical 17β-estradiol) = 0.1 mg active ingredient/g; Premarin® (topical CEE) = 0.625 mg active ingredient/g; Estragyn® (topical estrone) = 1 mg active ingredient/g