Hormone Therapy: Always a Hot Topic

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Hormone TherapyAlways a Hot Topic

• Suzanne Brandenburg MD
• Associate Professor of Medicine
• Program Director, Residency Training Program
• in Internal Medicine
• University of Colorado Denver
• July 17, 2008

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Outline

• Hormone Therapy
• Risks
• Benefits
• Treatment of Menopause
• Hormone therapy
• Alternative therapies
• Summary and Recommendations

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Hormone Therapy

• Until 2002, hormone therapy was routinely used to
  treat menopausal symptoms and was believed to
  improve long-term health.
• Then a large clinical trial, the Womens Health
  Initiative revealed health risks related to
  hormone therapy.
• What does this mean to you?

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Hormone Therapy Regimens

• For women who undergo menopause naturally,
  estrogen is prescribed as part of a combination
  therapy of estrogen and progestin. This is
  because estrogen without progestin increases the
  risk of uterine cancer.
• Women who undergo menopause as the result of a
  hysterectomy can take estrogen alone.

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Risks of Hormone Therapy

• The Women's Health Initiative found that women
  taking the combination estrogen-progestin,
  Prempro had an increased risk of developing
  certain serious conditions.
• According to the study, over one year, 10,000
  women taking estrogen plus progestin compared
  with a placebo might experience
• 7 more cases of heart disease
• 8 more cases of breast cancer
• 8 more strokes
• 18 more blood clots

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Risks of Hormone Therapy

• Over one year, 10,000 women (who has undergone
  hysterectomy) taking estrogen alone (Premarin)
  compared with a placebo might experience
• 12 more strokes
• 6 more blood clots
• The WHI found no increased risk of breast cancer
  or heart disease in this group.

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Risks Of Hormone Therapy

• Based on these numbers, the increased risk of
  disease to an individual woman is very small.
• However, the overall risk to menopausal women as
  a group became a substantial public health
  concern.
• Routine prescription of hormones at the time of
  menopause fell out of favor
• Many women abruptly stopped hormone therapy

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Risks Of Hormone Therapy WHI participants who
took hormone therapy may have increased cancer
risk even after discontinuing HRT

• Three years after stopping hormone therapy, women
  who took estrogen plus progestin during the WHI
  trial had a higher risk of cancer (particularly
  breast cancer) than women in the placebo group,
  according to a study published this spring
• 3 additional cases per 1,000 participants per
  year
• The groups had similar risks for cardiovascular
  disease and fractures.
• The cancer risk was still lower than at the end
  of the WHI trial.
• The authors recommend close surveillance of women
  for up to 8.5 years after stopping hormone
  therapy.

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Limitations of the Womens Health Initiative
(WHI)

• Does the WHI apply to the group that gains to
  benefit the most from Hormone therapy?

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Limitations of the Womens Health Initiative
(WHI)

• Only 12 of subjects were 50-54 years old
  (perimenopausal)
• Women who volunteered to participate were not
  likely to have severe symptoms
• Women with moderate to severe symptoms 3 months
  after discontinuing hormone therapy were
  discouraged from participating
• Average age of participants was 63 years
• Average age of menopause is 51 years

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Benefits of Hormone Therapy

• Estrogen remains the most effective treatment for
  troublesome menopausal hot flashes and night
  sweats.
• It can also ease vaginal symptoms such as
  dryness, itching, burning and discomfort with
  intercourse.

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The Estrogen ParadoxWomen appear to be
protected from heart disease until they go
through menopause

• Positive
• Improves lipids
• Improves flow-mediated vasodilation
• Improves fibrinolysis
• Antioxidant effects
• Negative
• Pro-coagulant effects
• Increases risk of venous thromboembolism
• Inflammatory response?

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Benefits of Hormone Therapy

• Long-term hormone therapy for the prevention of
  postmenopausal conditions is no longer routinely
  recommended.
• Women who take estrogen for short-term relief of
  menopausal symptoms may gain some protection
  against the following conditions
• Osteoporosis
• Colorectal cancer
• Heart disease
• Some data suggest that estrogen can decrease risk
  of heart disease when taken early in your
  postmenopausal years.
• The Kronos Early Estrogen Prevention Study
  (KEEPS) exploring estrogen use and heart
  disease in younger postmenopausal women is under
  way, but it won't be completed for several years.
  

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Menopausal Symptoms

• Hot flashes (HF) affect up to 60 of
  perimenopausal women
• Duration about 4 minutes, can occur up to 20
  times a day
• HF generally last for 6 months to 5 years
• A majority of women experience a cessation of
  symptoms within 2 years
• Rarely, symptoms can last up to 15 years

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Menopausal Symptoms

• Hot Flashes are worse in women who experience
  acute withdrawal of estrogen
• Following removal of ovaries (100 had symptoms
  after surgery, 90 lasted average of 8 years)
• Chemotherapy, tamoxifen and other treatment for
  breast cancer

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Menopausal Symptoms

• Vasodilatation and flushing of the skin
  followed by a feeling of intense heat
• Starts from the chest and progresses to the neck
  and face
• May be accompanied by sweating, anxiety,
  palpitations, and reddening of the skin

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Prescription Alternatives to Estrogen

• Hormonal Alternatives to Estrogen
• Progestins
• Androgens (testosterone)
• Tibolone
• Non-hormonal Alternatives to Estrogen
• Clonidine
• Venlafaxine
• SSRIs
• Gabapentin
• Veralipride

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Complementary Medicine Therapies

• 886 women were surveyed on methods tried to
  manage menopause
• Any therapy 22.1
• Stress management 9.1
• Alternative remedies 13.1
• Chiropractic 0.9
• Massage 2.6
• Dietary soy 7.4
• Acupuncture 0.6
• Naturopath/homeopath 2.0
• Herbalist 1.2
• 89-100 reported the therapies were somewhat to
  very helpful

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Phytoestrogens Soy Protein

• Interest in soy protein as treatment is based on
  epidemiological evidence that women with a
  lifelong diet rich in soy protein suffer less
  from hot flashes than women following a typical
  western diet low in soy protein.
• The cautious approach is to suggest that patients
  increase their consumption of soy-containing
  foods rather than high doses of supplements.

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Black Cohosh

• This native plant of eastern United States and
  Canada has been used in Germany for years to
  treat menopausal symptoms.
• The 1989 German commission E report and recent
  reviews in the German medical literature conclude
  that black cohosh diminishes the intensity and
  frequency of hot flashes.

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Unproven Botanicals OTCs

• Primrose Oil
• Ginseng
• Vitamin E
• Dong Quai
• Chinese Herbs

• DHEA
• Chaste tree
• Wild yam
• Licorice
• St. Johns wort
• Liu Wei Di Huang Tang

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Summary of Menopause Treatment Options

• Effective
• Estrogen
• Progestins
• Venlafaxine
• Clonidine
• Possibly effective
• Soy
• Black cohosh
• SSRIs
• Gabapentin
• Acupuncture and behavioral therapy
• Watch for
• Tibolone, Veralipride

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Weighing the Risks and Benefits of Hormone Therapy

• Hormone therapy is not the cure for aging that it
  was once believed to be
• It is still the most effective treatment for
  unpleasant menopausal symptoms for most women.
• If you're facing menopause, talk to your
  physician and make an individual decision about
  the benefits and the risks of short term hormone
  therapy.

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Recommendations

• Timing is everything
• Heart disease risk is probably not significantly
  raised in most healthy younger women.
• Based on previous data, the ongoing KEEPS study
  hopes to prove that estrogen may protect the
  heart when taken early in your menopausal years.
• Only initiate therapy if you are symptomatic
  around the time of menopause
• Aggressively treat heart disease risk factors
  such as high blood pressure and high cholesterol
• If possible, avoid hormone therapy if you have
• Heart disease
• Risk factors such as smoking or diabetes
• Increased risk of blood clots
• Increased risk of breast cancer

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Recommendations

• Minimize the amount of medication
• Use the lowest effective dose for the shortest
  amount of time needed to treat symptoms.
• On the other hand, don't be scared to continue
  treatment as long as you have debilitating
  menopausal symptoms.
• Find the best delivery method for you
• pill
• patch
• gel
• vaginal cream
• slow-releasing vaginal suppository or ring

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RecommendationsAreas of Uncertainty

• Is cyclic therapy better for women who need
  combined hormone therapy?
• What about micronized progesterone?
• Less negative impact on lipids
• Is Premarin better or worse than estradiol?
• Is oral or transdermal estrogen preferred?

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Final RecommendationsIf You Stop Hormone Therapy

• Layered clothing
• Air conditioning
• Lots of fans
• Wait until fall