Menopause

Question 1

What is natural menopause? Median age?

Answer 1

• permanent cessation of menses:
  defined retrospectively after 12 months of no menses, w/o any other explanation
• median age: 51.4
• elevated FSH not needed for dx in women over 45

Question 2

What does natural menopause represent?

Answer 2

• depletion of ovarian follicles manifested by low estrogen production, elevated FSH and loss of natural reproductive ability
• ovaries continue to make testosterone
• estrone (E1) is converted from androstenedione in fat cells

Question 3

What is surgical menopause? Premature ovarian insufficiency?

Answer 3

• surgical: removal of both ovaries b/f natural menopause

- premature ovarian insufficiency: menopause b/f age of 40

Question 4

What is perimenopause?

Answer 4

• menopausal transition of about 4 yrs beginning around age 47
• wide fluctuations of estrogen, hot flashes, decreased ovulation and irregular menses

Question 5

What is menopause not influenced by? What is it influenced by?

Answer 5

influenced by:
genetics
smoking

not influenced by:
age of menarche
number of preg.
use of OCPs
race
socioeconomic status

Question 6

Menopause - S/Sxs: hot flashes? Influences?

Answer 6

• or night sweats
• incidence varies widely: may be influenced by BMI than race/ethnicity (lower BMI = more dramatic hot flashes)
• last 2-4 minutes, sometimes followed by chills
• may be accompanied by palpations
• represent thermoregulatory dysfxn at hypothalamus: sx women trigger mechanisms to dissipate heat at lower core body temp with inappropriate peripheral vasodilation

Question 7

Swan study - on duration of hot flashes?

Answer 7

• median duration 7.4 yrs with 4.5 of those years after final menstrual period
• 8-9% may have hot flashes more than 20 yrs beyond menopause

Question 8

Other signs/sxs of menopause?

Answer 8

• mood and memory changes
• skin, hair and nail changes: decreased skin thickness and elasticity, increased facial hair related to decreasing SHBG (due to low estrogen) causing increased free testosterone
• osteoporosis: estrogen receptors present in osteoblasts, bone density decreases 1-2%/yr vs 0.5% in perimenopause
• sleep disturbances independent of night sweats: 30-46%
• lipid changes: decreased good HDL (estrogen increases HDL), and increased LDL

Question 9

Menopausal signs and sxs: urogenital atrophy?

Answer 9

• vaginal dryness contributes to dyspareunia
• atrophic urethritis causing dysuria and frequency
• vulvar and vaginal tissues more easily irritated
• could also be from the loss of pelvic organ support and increased prolapse

tx: use an estorgen cream

Question 10

Dx menopause criteria?

Answer 10

• women over 45: dx by menstrual hx w/ or w/o menopausal sxs
  no reliable way to predict final period (FSH isn’t reliable)
• women 40-45: dx by menstrual hx but also get lab to r/o other explanations for menstrual changes (TSH, prolactin, hCG)
• women with hysterectomy/endometrial ablation: assess menopausal sxs, get FSH

Question 11

What are alternatives to estrogen for tx hot flashes?

Answer 11

• SSRIs and SNRIs:
  some block active metabolite of tamoxifen, clinical significance is uncertain
  randomized double blind studies show efficacy with:
  -venlafaxine (but withdrawal sxs)
  -paroxetine (brisdelle) FDA approved lower dose 7.5 mg
• fluoxetine
• some recommendations for citalopram/escitalopram
• gabapentin with predominantly night sxs
• cetirizine (zyrtec)
• clonidine (sig dry mouth, constipation and dizziness)

Question 12

Other integrative modalities for tx hot flashes?

Answer 12

- inconsistent studies:
soy (isoflavones)
black cohosh
acupuncture
paced respirations
wt loss
mind body therapies
CBT
hypnosis

Question 13

Diff forms of estrogen?

Answer 13

• pills
• transdermal: patches, gels and lotions, mist
• intravaginal: creams, tablet, and ring

Question 14

Benefits of estorgen for the menopause?

Answer 14

• control vasomotor sxs
• relief from urogenital atrophy sxs:
  dyspareunia
  recurrent UTI or urethritis
  irritation of vestibule
• maintain bone density: decreased hip fractures

Question 15

Oral estrogen increases hepatic production of?

Answer 15

• TBG (so pt may need icnreased dose of levothyroxine)
• CBG
• SHBG (less free testosterone)
• triglycerides (can use transdermal - if high TGs - no first pass effect)
• HDL
• clotting factors

Question 16

Progestins used in menopause?

Answer 16

• medroxyprogesterone acetate
• micronized oral progesterone (doesn’t get broken down in GI)
• levonorgestrel- releasing IUD: not approved in US for endometrial protection

Question 17

When is hormone therapy beneficial?

Answer 17

• benefits outweigh risks:
  w/in 10 yrs of onset of menopause
  or less than 60
• hypothesis is that if continue to have estrogen - it has anti-inflammatory effect but if you haven’t had it for awhile and then take MHT it will have inflammatory effect
• have to look at pt as a whole: sxs, personal health hx, smoking, wt, cholesterol, DVTs

Question 18

Risk of other diseases with menopause hormone use?

Answer 18

• risk of CHD appears to be influenced by age of exposure to estrogen: no excess risk and possible cardioprotection with use immediately after menopause
• roles of estrogen vs progestin in breast cancer uncertain: in WHI trial - no increased breast cancer in estrogen only group but was seen in estrogen progestin group

Question 19

What form of progesterone is preferred in MHT?

Answer 19

micronized progesterone rather than progestins like medroxyprogesterone acetate is preferred b/c:

• assoc with lower risk of thromboembolism, stroke and elevated TGs
• hasn’t been assoc with increased risk of breast cancer or CHD

Question 20

Is there FDA approved testosterone for women? What levels of estrogen should the pt start at?

Answer 20

• no, no FDA approved testosterone

- start at lowest dose of estrogen and increase as needed

Question 21

How do you decide on tx vehicle for MHT?

Answer 21

• is goal vaginal effect only or helping hot flashes (systemic) too?
• if using systemic: cyclic (have menses) or continuous
• oral or transdermal delivery
• synthetic progestin or natural progesterone if uterus is present (synthetic may not be good for brest health - use natural, don’t use daily, our bodies don’t make this daily)

Question 22

If sxs of urogenital atrophy are only bothersome sx of menopause what should be used?

Answer 22

• only use local estrogen rather than systemic

Question 23

What works the best for vasomotor sxs of menopause?

Answer 23

• estrogen! Nothing works as well

- but consider other approaches first (SSRIs)

Question 24

A woman with a uterus needs what else if receiving estrogen?

Answer 24

• also needs progestin to protect endometrium from unopposed estrogen which increases risk of hyperplasia and cancer

Question 25

What is the safer - transdermal or oral estrogen?

Answer 25

• transdermal: less stimulation of clotting proteins by avoiding the first pass effect = lower risk of VTE and stroke

Question 26

When is endometial sampling done?

Answer 26

• b/f starting therapy in woman with irregular bleeding
• any woman on continous therapy who spots or bleeds after 6 mos
• bleeding or spotting after a yr of amenorrhea in woman not on hormones
• endometrial hyperplasia or cancer can occur w/in 6 mos of starting unopposed estrogen

Question 27

What other meds can cause flushing or night sweats?

Answer 27

• SSRIs, SNRIs, TCAs
• triptans
• antipyretics: ASA, acetaminophen, NSAIDs
• SERMs: raloxifene, tamoxifen
• insulin, sulfonylureas
• beta agonists
• alcohol
• BBs, CCBs
• omeprazole

Question 28

What disorders may cause flushing or night sweats?

Answer 28

• lymphoma
• solid tumors: germ cells, prostate cancer, RCC
• infections: TB, bacterial - endocarditis, osteomyelitis, Viral - hep C, HIV
• endocrine: carcinoid syndrome, DI, hyperthyroidism, hypoglycemia, pheochromocytoma
• neuro disorders: autonomic neuropathy, stroke
• chronic fatigue sydrome, GERD, mastocytosis, panic disorder, sleep apnea, temporal arteritis