Estrogen Progesterone Testosterone

1
Postmenopausal Ovary

• Estrogen Progesterone Testosterone
  

2
Consequences of low estrogen

• Symptoms hot flashes, vaginal dryness, cognitive
  problems ?
• Bone loss Osteoporosis
• Heart disease

3
When can women take estrogen?

• Perimenopause, early menopause for symptoms.
  Eventual taper.
• Taking very small risk (DVT/stroke) to use
  estrogen for a specific indication for which
  there is proven benefit (like taking any
  medication). Overall risk-benefit neutral.
• Should not be used to prevent heart
  disease/dementia
• Vaginal estrogen an option for many women
• POF

4
Perimenopausal Woman urinary hormones x 6 mo
FSH (mIU/mgCr)
LH (mIU/mgCr)
PDG (ug/mgCr)
E1 (ng/mgCr)
0 20 40 60 80 90 110
130 150 170
DAYS
from Santoro et al, JCEM 1996
5
Hot flashesChange in thermoregulatory set-point
Estrogen
6
Reduced Thermoneutral Zone
Temperature elevation ? hot flash
Kronenberg F, et al. Maturitas 1984 Freedman
RR. Am J Hum Biol 2001
7
Menopausal symptoms

• SWAN (Study of Women Across the Nation)
• 3200 women, longitudinal study across menopausal
  transition
• Ethnic and socioeconomic diversity
• Symptoms specific to menopause
• Vasomotor symptoms, vaginal symptoms, sleep
  disturbances
• Other Anxiety, fatigue, joint pains, memory loss

8
Vasomotor symptoms SWAN

• Hot flashes are most common in late menopausal
  transition (75)
• In US Prevalence in African-American Caucasian
  Hispanic, Japanese, Chinese
• More common with obesity, surgical menopause,
  smoking, stress, low socioeconomic status, less
  education

9
Vasomotor symptoms

• Average duration 85-90 resolve within 4-5 years
• 10-15 have persistent symptoms for many years

10
Vasomotor symptoms Estrogen

• E reduces frequency by 80-95 (dose-dependent)
• All types and routes are effective
• Short-term therapy (up to 5 years)

11
Stopping estrogen

• WHI
• EP vasomotor symptoms after stopping in 55 if
  history of symptoms at baseline
• Placebo 21 if sx at baseline
• Most women then tried alternative
  therapies (Ockene JAMA 2005)
• Taper versus stopping abruptly?
• Quality of life lowest dose possible

12
Bioidentical Hormones NOT SAFER!

• Bioidentical or natural hormones
• Term refers to individualized preparations of
  steroid hormones (E,P,T) compounded as creams,
  gels, pills, or suppositories
• Baseline saliva or blood tests
• Lack of quality control
• No evidence that they are more effective or safe
• Profit driven not in best interest of women
  very expensive

13
Other hormone therapies

• High dose progestins medroxyprogesterone (400 mg
  IM or 40 mg po/day), megestrol (20-80 mg)
• Tibolone Synthetic steroid with estrogenic,
  progestagenic, androgenic effect --- Benefits
  hot flushes, bone mineral density,?sexual
  function --- Concerns vaginal bleeding, CVD,
  breast cancer

14
SSRIs

• Majority of studies in women with breast ca
• Paroxetine CR 20 mg 2 trials modest effect
• Venlaxafine 75 mg inconsistent
• Meta-analysis of 7 trials, (-1.13 flush/day vs
  placebo) (Nelson JAMA 2006)
• Other drug for hot flashes clonidine
• For sleep Eszopiclone

15
Gabapentin
Bedtime dose, REM sleep Pandya Lancet 2005
16
Phytoestrogens SERMs

• Phytoestrogens isoflavones, lignans, coumestans
• Surveys of use among PMW
• Cultures with lifelong high-soy diets
• Benefits of starting at menopause -- Dietary
  soy may have modest hot flash benefit --
  Isoflavone preparations seem to be less
  effective (concentrated supplements)
• Concerns about phytoestrogens and breast

17
Behavioral and alternative therapies

• RCTs What works?
• Vitamin E decreases one flush/day (not clinically
  important) (Grady NEJM 2006)
• Paced respiration better than relaxation
• What doesnt work?
• Yoga, Chinese herbs, dong quai, primrose oil,
  ginseng, kava, red clover extract
• Exercise
• Black cohosh HALT trial no more effective than
  placebo. CEE effective as expected.

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Genitourinary symptoms

• Symptoms
• Vaginal dryness, painful intercourse, urinary
  symptoms
• At least 50 in late menopause, if untreated,
  symptoms persist or worsen
• Vaginal estrogen
• More effective than taking it by mouth or patch
• Very little absorbed if correct dose used.

19
Vaginal estrogen Standard dose

• Estrogen creams
• Dose1 to 4 gm (1/4 to full applicator)
• 1 gm E2 cream contains 100 ug E2
• Increase in serum E concentrations, suppression
  of LH, FSH
• Need for progestin

20
Vaginal estrogen Low dose

• Vaginal estradiol tablets 10 ug, 25 ug
• Administered nightly x 2 wks then 2-3x weekly
• Vaginal ring (Estring) 8-9 ug/day
• No significant endometrial thickening
• Serum estrogen concentrations increase slightly

21
Vaginal estrogen

• Safe for breast cancer patients?
• Serum E concentrations increase slightly, but
  remain in postmenopausal range. Impact on
  recurrence unknown
• Safe for meningioma patients?

22
Non-estrogen options
Moisturizers Nonhormonal bioadhesive
longer-term use Lubricants OTC water-based
liquids and gels