Phillips - Menopause

Question 1

What is menopause?

Answer 1

• 1 year without menses and FSH >30 (because estrogen goes down)
• NOTE: women now spend about 40% of their lives in menopause, which begins around ag 45-55

Question 2

What is perimenopause?

Answer 2

• Age group near menopausal age, 45-55
• With symptoms: menopausal transition

Question 3

What is post-menopause age group?

Answer 3

• Postmenopause: beyond menopause, or age >55

Question 4

What is the biology of menopause?

Answer 4

• End of reproductive life about age 43
• Ovary continues to produce eggs sporadically, but they are abnormal
• With ovulation, estrogen still being produced, but in lower amounts (no progesterone)
  1. With less amounts of estrogen being produced, FSH rises
  2. Menses becomes less frequent, lighter
• Menopause defined as:
  1. No menses for a year
  2. FSH >30 (bc estrogen levels go down)

Question 5

What things bring women to the OB to begin hormone therapy (bar chart)?

Answer 5

Question 6

What are the symptoms of menopause?

Answer 6

• Most common: hot flashes -> skin changes and vasodilation have been documented
• May report waking up at night with sweats, then cooling effect -> may happen 5x/night, and disturb sleep
  1. If no treatment, will dissipate
• Vaginal atrophy (can cause dyspareunia): late effect, but can tx w/estrogen, vaginal or systemic
• Probably due to gonadotropin spikes as much as estrogen deficiency
• May occur as peri-menopausal symptoms

Question 7

What are the FDA-approved indications for HRT?

Answer 7

• Indicated for:
  1. Treatment of moderate-to-severe vasomotor symptoms associated with menopause -> 1^o indication, and most common reason women start therapy
  2. Treatment of vulvar and vaginal atrophy: topical vaginal products should be considered
  3. Prevention of postmeno osteoporosis: FDA encourages consideration of non-estrogen meds when HT is prescribed solely for the prevention of postmenopausal osteoporosis

Question 8

What are the options for post-meno HRT?

Answer 8

• Estrogen: can be taken alone only by women who have had a hysterectomy
  1. Estradiol pill, transdermal patch, or gel
  2. Conjugated estrogens: Premarin
• Progestin added: for pts that have a uterus, to prevent endometrial hyperplasia and cancer:
  1. Medroxyprogesterone
  2. Micronized progesterone

Question 9

What symptoms are erroneously associated with menopause?

Answer 9

• Depression
• Lack of interest in sex
• Going crazy

Question 10

How should post-meno women with vaginal complaints only be treated?

Answer 10

• Examples: dryness, dyspareunia
• Preferred tx is low-dose, vaginal estrogen; FDA-approved use
• NO need for progestins

Question 11

What 3 medical illnesses are associated with menopause?

Answer 11

• Osteoporosis
• Heart disease
• Cancer

Question 12

Can estrogens be used to treat osteoporosis?

Answer 12

• NO -> only used to prevent osteoporosis
  1. Individual risk factors
  2. Screening via BMD msmts starting at 65-y/o
  3. Should have another indication for HRT
  4. Affects osteoclast and osteoblast activity: even low-dose estrogen therapy can INC BMD
• Tx is bisphosphonates

Question 13

Who is at high-risk for osteoporosis?

Answer 13

• High-risk groups:
  1. Caucasian/Asian
  2. Thin
  3. Smoker, alcohol Use
  4. Steroid Use
  5. Family History

Question 14

Describe the effects of combo and estrogen HRT on fracture risk.

Answer 14

• Significant reduction in hip, vertebral, and all fractures in Women’s Health Initiative study

Question 15

How does estrogen affect CV risk?

Answer 15

• Women protected from CVD until menopause (when compared to men)
• Early loss of endogenous estrogen (via oophorectomy or premature ovarian failure, for example) is associated with CVD
• Endogenous estrogen INC smooth muscle proliferation, lowers cholesterol, and improves vascular tone
• Remember: also associated with VTE, PE

Question 16

What is the natural history of CVD in most women?

Answer 16

• 35-y/o: fatty streaks + minimal atherosclerotic plaques
• 45-55: active progression of lesions (menopausal transition)
  1. 5-8 yrs post-meo: INC in plaques and intima-media thickening
• > 65: complications start to develop, and women’s rate is equal to men’s
• NOTE: statins and ASA may not have the same benefit in women that they do in men

Question 17

What did the WHI study conclude about HRT and CVD risk? How might the study design have influenced this result?

Answer 17

• RCT that concluded: INC risk of CHD in HRT users versus those on placebo
• However, women recruited were 50-79-y/o, and average age was 64-y/o -> likely already had CHD if they were over age 65
• Only 10% were between 50 and 54, and 20% were b/t 54 and 59, or near menopausal onset
• Theory that HRT has (+) effects when initiated peri-menopausally, but (-) effects when started post-menopausally

Question 18

How does menopausal status affect the CV effects of HRT?

Answer 18

• Peri-menopausal use: positive effects on vascular remodeling -> DEC intimal thickening, and DEC incidence of plaques
• Post-menopausal use: in women >65, plaques already formed, and the thrombogenic effects of estrogen clot off the artery
  1. AE’s in first year of use: MI’s in year 1 -> may have already had heart disease
• STRATIFICATION by YEARS AFTER MENO: # of events INC with years since menopause
  1. <10: 0.76 HR; >10: 1.10 HR; >20: 1.66 HR

Question 19

Ms. R comes to you as a 40 y/o who recently had a TAH-BSO (removal of ovaries and uterus) for adhesions and pain. Because of her family hx of CHD, her surgeon would not put her on ET. She is having night sweats and is “miserable.”

Your thoughts?

Answer 19

• This woman can definitely take hormones (“needs to be on them”)
• Premature ovarian failure, or oopherectomy pre-menopausally associated with CHD
• No personal history of CHD; statins are not a contraindication for ET
• Do lipid profile and TREAT -> ESTROGEN
• Maybe use non-oral formula (transdermal), but E only because she has had a hysterectomy
  1. Vaginal estrogen not absorbed systemically, so progesterone not needed
• If she is 40, and needs hormone support, she could be on estrogen for 15 years because pre-menopausal (danger is in post-menopausal women)

Question 20

Is ET recommended as a therapy for coronary protection?

Answer 20

• NO, but if woman comes in with premature ovarian failure -> give her estrogen if she wants to be on HRT
• NOTE: Dr. Phillips also presented a study that said depriving estrogen to women has cost lives due to the ability of ET to reduce mortality in women with a hysterectomy

Question 21

What did WHI say about ET/EPT and risk of thrombotic events and colon cancer?

Answer 21

• INC risk of DVT
  1. 50-59: no INC risk of stroke for ET/EPT
  2. 60-69: INC risk of stroke for ET (HR: 1.62)
• Estrogen DEC risk of colon cancer

Question 22

What is the consensus on ET and risk of breast cancer?

Answer 22

• Complex issue
• INC risk in breast cancer in 3-5 yrs of continuous EPT therapy, but it may be the progestin that adds the risk
• Risk is small, and DEC after HT is stopped
• NOTE: only recommendation out there about an absolute age is that women should come off of these at age 65 because most women have heart disease by that time

Question 23

So, how should you treat pts coming in with complaints of menopausal symptoms?

Answer 23

• Individual decision in terms of QOL and health priorities
• Pt w/family hx of breast cancer (or a smoker) may make different decision than healthy woman w/bad hot flashes and no history -> INDIVIDUALIZATION IS KEY
  1. Options should be given depending on personal risk factors or health priorities
• Take symptoms seriously and talk about treatment options -> treat women who want HT, but review risks, benefits, and alternatives

Question 24

22-y/o smoker comes in and wants OC estrogen. Can she take it?

Answer 24

• Yes!
• If you are 35 and older, you can’t be on estrogen; if she is 22, then she can
• This will NOT increase her risk of heart attack and stroke more than just smoking
• Do NOT put older, heavy smoker on estrogen -> look for alternatives, like SSRIs to relieve menopausal symptoms