menopause

Question 1

what are indications for HRT

Answer 1

• moderate to severe vasomotor symptoms

Question 2

contraindications to systemic HRT

Answer 2

• pregnancy
• estrogen responsive tumor (EMCA or breast)
• history of VTE
• active severe liver disease
• unexplained vaginal bleeding
• coronary artery disease
• stroke
• dementia

Question 3

what was primary outcome and primary adverse outcome of WHI? what were groups being compared?

Answer 3

• primary outcome: ASCVD (MI, acute coronary death_

- 3 arms: placebo vs combination HRT (CEE 0.625 mg + MPA 2.5 mg/day) vs CEE 0.625 mg daily

Question 4

what was the primary outcome of the WHI trial?

Answer 4

no increase in overall mortality in the HRT or ERT groups compared to placebo (i.e. it is not indicated for primary prevention of ASCVD)

Question 5

what were the primary/secondary outcomes of combination HRT

Answer 5

risks:
- 30% increased risk of coronary heart disease
- 25% increased risk of breast cancer
- 40% increased risk of stroke/PE
(all into 7-8 more cases/10,000 women year)

benefits:
- 33% reduction in bone fracture
- 33% reduction in colon cancer
(5-6 fewer cases/10,000 women years)

Question 6

what are the current risks of combination HRT

Answer 6

• VTE
• breast cancer
• biliary issues
  Starting cHRT >60 years (NAMS 2017 guidelines)
• MI, stroke, dementia

Question 7

what were the primary/secondary outcomes of estrogen alone therapy in WHI?

Answer 7

risk:

• increased VTE/stroke
• NO DIFFERENCE IN CHD, BREAST CANCER

benefit:

• decreased fractures (38-39%)
• NO DIFFERENCE IN CRC RATES

Question 8

what is the caveat to WHI findings

Answer 8

mean age was 63 years. HERS study and subsequent analyses found no CV risk in age under 60 years

Question 9

okay to use HRT in women who undergo ppx BSO for BRCA?

Answer 9

limited observational studies say okay to age 52

Question 10

okay to use HRT in family hx of breast cancer?

Answer 10

HRT does not appear to increase risk

Question 11

endometrial and breast cancer survivors?

Answer 11

• try non-hormonal first

- level II that it does not increase risk, and has minimal systemic absorption

Question 12

key concepts in treatment

Answer 12

• lowest dose possible of HRT
• only for VSM or GSM
• not hard and fast rule to dc at age 65
• consider transdermal for pts with

Question 13

what are doses/options for estrogen component and progesterone component?

Answer 13

standard dose

• conjugated estrogen: 0.625 mg/day
• micronized estradiol 17B 1 mg/day
• transdermal estradiol 0.0375-0.05 mg/day

low dose

• conjugated estrogen: 0.3-0.45 mg/day
• micronized estradiol 17B 0.5 mg/day
• transdermal estradiol 0.025 mg/day

progestins - only for uterine protection

• MPA 2.5 mg/day or 5 mg x 12 days cycled (starting day 1 or 16)
• micronized progestin 100 mg/day or 200 mg/day x 12 days

possible to use estrogen agonist/antagonist with estrogen
- conjugated estrogen 0.45 mg + bazedoxipene 20 mg/day combination tablet

Question 14

what are treatment options for GSM?

Answer 14

• estradiol 17B ring: releases 7.5 mcg/day; replace q3 months
• estradiol ring: 0.05 mg/day
• estradiol 17B cream: 0.05 mg/day (estrace)
• CEE cream: 2/gday (premarin)
• vaginal estradiol tablet 10 mcg tabs (estrace)
• vaginal inserts (4 nanogram or 10 nanogram) - vagifem

all creams/tabs - daily x 2 weeks, then twice weekly

Question 15

what are non-hormonal options for VSM/GSM?

Answer 15

non-pharmacologic:

• sleeping in cool area
• dress in layers
• avoid hot foods, beverages, spicy food, ETOH, caffine
• Consume soy products
• increase H2O

all more effective than placebo but less than HRT
SSRIs/SNRIS:
- paroxetine (brisdelle) - only FDA approved at 7.5 mg/day
- fluoxetine (prozac)
- venlafaxine (effexor)
-AVOID PAROXETINE AND FLUOXETINE WITH TAMOXIFEN, CYP2D6 inhibitor (may dampen tamoxifen’s effect)

Clonidine
- 0.1 mg/day, watch hypotensoin

Gabapentin (600-900 mg/day)
- similar efficacy to venlafaxine, pts prefer venlafaxine

SERM

• Ospemifene 60 mg/day
• FDA approved for GSM with dsyapruenia
• no increased risk of EMCA/hyperplasia
• risks of muscle spasm, vaginal discharge, VSM

Vaginal lubricants: water or silicone based