Menopause Hormone Therapy

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Menopause Hormone Therapy Powered By Docstoc
					Menopause Management

  Christiane Kuntz M.D. C.C.F.P. F.C.F.P.
       Academic Day – FM residents

             August 24, 2007
Women’s Health Initiative Trial
• Prospective randomized controlled trial in 40 US centers
  designed to assess the effect of systemic hormonal
  therapy on the rates of occurrence of various chronic
  diseases in postmenopausal women and to last 8 years
• Outcomes being assessed included coronary heart
  disease (CHD), breast cancer, venous thromboembolic
  disease, stroke, colorectal cancer, uterine cancer,
  osteoporotic fractures, dementia and death
• Highly symptomatic women were deliberately excluded
  from the study
Women’s Health Initiative Trial
• JAMA, July 17, 2002 – Vol. 288, No. 3
• 16,608 women, average age 63 (ages 50-79), intact uterus,
  randomly assigned to receive conjugated equine estrogen .625 mg
  and medroxyprogesterone 2.5 mg (Premplus) on a continuous basis
  vs. placebo; trial discontinued prematurely after 5.2 years
• Treated women had an absolute increased risk of <.1% per year of
  use for the following undesirable outcomes: invasive breast cancer,
  stroke, heart attack and pulmonary embolus
• Hazard ratio (with 95% confidence interval) for CHD 1.29 (1.02-
  1.63), stroke 1.41 (1.07-1.85), PE 2.13 (1.39-3.25), breast cancer
  1.26 (1.0-1.59), colon cancer 0.63 (0.43-0.92), uterine cancer 0.83
  (0.47-1.47), hip fracture 0.66 (0.45-0.98), death 0.98 (0.82-1.18),
  global index (excess risk for all monitored events) was 1.15 (1.03-
  1.28), an insignificant 2 events per 10,000 person years
Women’s Health Initiative Trial
• JAMA April 2004;291:1701-12
• Results for study of 10,739 hysterectomised women treated with
  conjugated equine estrogen .625 mg alone (Premarin) or placebo
  for almost 7 years
• Main outcomes showed no statistically significant difference in risk
  for CHD, a slightly decreased risk for breast cancer, a <.1% annual
  absolute increased risk for stroke and venous thromboembolic
  disease in the treated women as well as the previously seen benefit
  for prevention of osteoporotic fractures and bowel cancer
• Hazard ratio (with 95% confidence interval) for CHD 0.91 (0.75-
  1.12), breast cancer 0.77 (0.59-1.01), stroke 1.39 (1.10-1.77), PE
  1.34 (0.87-2.06), colorectal cancer 1.08 (0.75-1.55), hip fracture
  0.61 (0.41-0.91), death 1.04 (0.88-1.22) and global index 1.01
Symptoms, Signs & Issues:
•   Irregular bleeding   • Decreased libido
•   Hot flashes          • Skeletal system
•   Sleep disturbances       effects
•   Vaginal atrophy      •   Cardiovascular effects
•   Urinary concerns     •   Weight gain
•   Headaches            •   Hair changes
•   Mood fluctuations
Irregular bleeding:

• Rule out organic causes
• Consider endometrial biopsy
• Consider transvaginal pelvic ultrasound –
 if lining < 5 mm relax
Irregular bleeding – Rx options:
• Cyclic progesterone    • D & C (out of favor)
• Oral contraceptives,   • Endometrial
    patches, rings           ablation/resection
•   Tranexamic acid      •   Uterine artery
    (Cyklokapron)            embolisation (fibroids)
•   NSAIDs               •   Progesterone-
•   GnRH agonists            impregnated IUS
•   Danazol
Hot flashes Rx:

• Systemic estrogen – 80% efficacy
• Systemic progestins – 80% efficacy
• SSRI/SNRI – about 50% efficacy
• Gabapentin (Neurontin) – 50% efficacy
• Deep breathing exercises – 40% efficacy
• Placebo – up to 40% efficacy
• Clonidine – 30% efficacy
Hot flashes Rx continued…
• Bellergal Spacetabs – 30% efficacy (belladonna,
    ergotamine, phenobarbital)
•   Vitamin E – 10-20% efficacy
•   Black cohosh, red clover – more effective than
•   Evening primrose oil, soy proteins, dong quai,
    ginseng – no more effective than placebo
•   St. John’s wort, chastetree, combination
    products – not studied in the menopause
•   Kava – may be useful, but hepatotoxic
Sleep disturbances Rx:

• Same as usual, including good sleep
  hygiene techniques
• Antidepressants - low dose sedating ones
  like trazodone 25-50 mg qhs; SSRI/SNRI
• Benzodiazepines with short half-lives
• Systemic estrogen therapy
Vaginal atrophy Rx:

• Vaginal lubricants (Oh My, Slippery Stuff,
  KY jelly, Astroglide)
• Vaginal moisturisers (Replens)
• Estradiol-impregnated ring (Estring)
• Estradiol vaginal tablets (Vagifem)
• Vaginal estrogen creams (use cautiously)
• Systemic estrogen therapy
Urinary concerns Rx:
•   avoid bladder irritants   • anticholinergics for urge
•   avoid fluid restriction       incontinence
•   good perineal hygiene     •   pessaries
•   Kegel exercises           •   cranberry juice to
•   Biofeedback                   decrease UTI risk
•   timed voiding             •   surgery – last resort
                              •   *conjugated equine
                                  estrogen not helpful for
                                  prevention or relief of
                                  urinary incontinence
Headache Rx:
• Avoid triggers
• Analgesics – NSAIDs, acetaminophen,
  narcotics (avoid these if possible)
• Abortive treatments – triptans
• Prophylactic treatments
• Antidepressants
Mood problems Rx:

• Decrease stress
• Exercise
• Light therapy (especially if seasonal Sx)
• Systemic estrogen
• Antidepressants – SSRIs, SNRIs, NaSSAs,
Decreased Libido Rx:

• Counselling – exploring underlying issues
• Systemic estrogen
• Androgen therapy (only in conjunction
 with systemic estrogen in menopausal
Skeletal system effects Rx:

• Lifestyle changes: exercise, calcium,
  vitamin D, avoid ETOH, avoid smoking,
  avoid caffeine, avoid medications bad for
  bone health
• Bisphosphonates
• Systemic hormonal therapy effective but
  only to be used if required for Sx control
Cardiovascular effects:
• Hormonal therapy no longer indicated for
    primary or secondary prevention
•   Systemic estrogen is relatively contraindicated
    but is used in a small percentage of cases in a
    transdermal form for very severe Sx which are
    not responding to non-hormonal alternatives
•   Women with hypertension, smokers should also
    be treated with transdermal estrogen and
    progesterone or with oral micronised
    progesterone rather than with medroxy-
    progesterone acetate
Weight gain:

• Not felt to be related to menopause or
  systemic hormonal therapy
• Likely due to aging and lifestyle
Hair changes:

• Hair thinning and hirsutism not specifically
  related to menopause
• Likely related to genetic factors and a
  change in the hormonal balance of
Basic Principles of Hormonal Rx
• Perform complete initial assessment
- history (including review of risk factors)
- physical exam (including BMI, BP, breast
  and pelvic assessment)
- Blood work (including CBC, lipids, TSH,
  FSH, glucose, liver enzymes)
- ancillary tests ie. mammography, BMD,
  pelvic US if indicated
Basic Principles continued...
• Use HT primarily for symptom control
• Use lowest effective dose
• Use HT for the least amount of time
• Use safest HT formulations (theoretically
  transdermal) especially for higher-risk
• Do not use HT for cardioprotection
  (primary or secondary)
Basic Principles continued…
• Do not use HT as first-line treatment for
• Do not use HT to prevent dementia
• Do not initiate HT in older women (in 60’s
  and 70’s)
• Use progestogen in women with an intact
• Do not use progestogen in
  hysterectomised women
Basic Principles continued…

• Monitor the endometrium when
• Switch from BCP to HT in early 50’s if
• Can stop HT “cold turkey” or taper dose
• Start with CS-EPT in freshly menopausal
  women to avoid dysfunctional bleeding
Basic Principles continued…

• HT duration depends on a well-informed
  and counseled patient, your medical
  judgment re: the risk/benefit ratio for that
  woman, and your awareness and
  application of the most recent evidence-
  based literature on HT
• At minimum, once the patient is stable,
  review her HT treatment with her annually
HT Formulations:

Estrogen – oral
• Conjugated equine estrogen (Premarin)
• Synthetic conjugated estrogen (Congest,
  CES, PMS-conjugated)
• Esterified estrogens (Neo-Estrone)
• Estropipate (Ogen)
• 17 beta-estradiol (Estrace)
HT Formulations continued…
Estrogen – transdermal
17 beta-estradiol matrix patch
• Climara – changed 1X/week
• Oesclim – changed 2X/week
• Estradot – changed 2X/week
17 beta-estradiol reservoir patch
• Estraderm – changed 2X/week (patch should not
  be cut)
17 beta-estradiol transdermal gel
• Estrogel – applied daily
HT Formulations continued…
Estrogen - vaginal
• conjugated equine estrogen (Premarin)
• estropipate (Ogen)
• esterified estrogen (Neo-Estrone)
• 17 beta-estradiol (Estring)
• estradiol hemihydrate (Vagifem)
HT formulations continued…
• medroxyprogesterone acetate (Provera)
• norethindrone (Micronor)
• micronised progesterone (Prometrium)
• levonorgestrel (Mirena)
HT Formulations continued…
Combination EPT
oral continuous-combined regimen
• conjugated equine estrogen + medroxyprogesterone
   acetate (Premplus)
• ethinyl estradiol + norethindrone acetate (Femhrt)
transdermal continuous-combined regimen
• 17 beta-estradiol + norethindrone acetate (Estalis)
transdermal continuous-sequential regimen
• 17 beta-estradiol + norethindrone acetate (E alone for 2
   weeks followed by E + P for 2 weeks, cycle repeated)
   (Estalis Sequi, Estracomb)
HT Formulations continued…

Oral - Testosterone undecanoate (Andriol)
Transdermal – testosterone gel (Androgel);
  patches (Androderm) (unstandardised for
  use in women)

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