211. Menopause/HRT

Question 1

Define the following:

• Menopause
• Primary Ovarian Insufficiency
• Menopausal Transition (cardinal signs/sx)
• Perimenopause

Answer 1

MP: FMP in woman due to ovarian aging/loss of follicles

• dx AFTER 12mo of amenorrhea (retro-dx)
• ave age 51/52

POI: FMP in woman <40yo

MP transition: time of waning ovary fx leading to FMP

• avg onset 47.5yrs, lasts 4 yrs
• sx: menstrual cycle change, VMS, sleep disturbance, mood changes, vaginal dryness, dyspareunia

Peri-mp: mp transition + FMP (MP) + 1st post-mp year

Question 2

What occurs to the HPO axis at the time of MP?

What is the KEY post-MP finding?

Answer 2

• Follicle Depletion = low inhibin B (loss negative feedback)
• HIGH FSH (due to low inhibin B)
• initial increase in E (irregular heavy bleeds)
• low AMH (low follicle count)
• unremitting follicle depletion with E decline
• permanent amenorrhea with high FSH, low E

Key Finding: ELEVATED SERUM FSH (using estrogen is least helpful due to variability)

Question 3

What are the VMS of MP? What is the physiology of these VMS? Natural hx of vms

Answer 3

VMS: recurrent transient episodes of flushing, sensation of heat from upper body, face, neck, spreads outward; increased HR, palpitations, +/- anxiety, sweating, chills

• obesity is RF, smoking/alcohol assoc with more VMS sx
• due to narrowed thermoneutral zone in hypothalamus (E helped keep body in good range) - occurs with low E not helping thermoregulate anymore
• sx are SELF LIMITING

Question 4

Besides VMS, what 3 other key signs of MP should you look out for?

Answer 4

1. Depression: 2x risk in baseline, risk returns post-mp, NEED TO SCREEN
2. Osteoporosis: low BMD, architectural deterioration of bone tissue, high fracture risk (E used to increase oclast apoptosis, decrease oclast differentiation)
   - E replacement maintains BMD
   - screen BMD with DEXA scan
3. Coronary Heart Disease: leading cause of death in women, incidence in women inflects at mp age
   - mech: low E = higher total Chol, LDL, TG; more VC; more ins resistance
   - E replacement is beneficial ONLY EARLY in mp (decreases atherosclerotic prevention); LATE use IS DETRIMENTAL (destabilizes plaque)

Question 5

What are 5 contraindications for HRT

What are 3 main indications for HRT

What are the FDA indications for HRT (4)

What is the prognosis for mp sx

Answer 5

CI: Hx of breast cancer, CHD, previous VTE, active liver disease, unexplained vaginal bleeding (sign of endometrial cancer)

HRT: severe VMS affecting QoL, <10yrs from LMP and/or <60yo

FDA: VMS, prevention of bone loss, hypoestrogenism (hypogonadism, POI, surgical mp), vulvovaginal atrophy/GSM (topical first then systemic)

Prognosis: VMS resolve over time in most women (10 yrs), local vulvovaginal sx do not resolve w/o tx and may be progressive

Question 6

Tx for:

• mp sx
• non-conventional mp sx tx
• local vulvovaginal sx
• depression
• bone loss

Answer 6

mp

• conservative measures: lower room temp, wear layers
• systemic E: most successful by widening thermoneutral zone (lowest dose and titrate up)
• use E with P if still have uterus - protect uterus from unopposed E (reduce risk of endometrial cancer)

non-E tx:

• SSRIs: Paroxetine, Escitalopram (AVOID in breast cancer patients on Tamoxifen)
• SNRIs: Venlafaxine
• Gabapentin
• Clonidine

VVS

• non-E: regular sex, lubricants, moisturizers
• topical E
• Ospemifene: SERM

Depression

• return to baseline risk post-mp
• antidepressants adjunct

Bone loss: HRT may prevent bone loss, but avoid HRT risk with other meds instead