Discontinuation of Study Medication: Guidance From the WHI

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Discontinuation of Study Medication Guidance
From the WHI

• Susan L. Hendrix, DO
• Gynecology and Menopause
• Wayne State University School of Medicine

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How We Informed Participants

• Priority was to our participants
• First to Know commitment from the Investigators
• Letters were written by Dr. Lenfant and
  centrally mailed to all E plus P participants to
  arrive on Monday, July 8th
• Coordinated with the July 9th press conference
• Press conference July 9th coordinated with JAMA
  for release of study findings to physicians
• Press conference reported findings
• JAMA express full article posted on web site
  July 9th
• WHI Website posted July 9th
• JAMA article
• Questions and answers

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The Unblinding Process

• Stop taking your study pills. Most of you will
  probably have no effects from stopping your
  pills. Some of you may have some menopausal
  symptoms like hot flashes, or you may have mild
  spotting or bleeding. These symptoms should
  decrease over time. Please contact your clinic if
  you have concerns.

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http//www.nhlbi.nih.gov/health/prof/heart/other/
menopaus/index.htm
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2.2 Symptom Prevention TreatmentVasomotor
Symptoms Hot Flushes Night Sweats

• 2.2.1 Lifestyle
• Wear layered clothing that can be removed or
  added as necessary
• There is conflicting evidence as to whether
  exercise improves menopause vasomotor symptoms
• 2.2.2 Diet
• Avoid hot spicy foods and beverages, and reduce
  caffeine
• Avoid alcohol beverages (excess can cause
  flushing)

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2.2 Symptom Prevention TreatmentVasomotor
Symptoms Hot Flushes Night Sweats

• 2.2.3 Pharmacotherapy
• In a systematic review of more than 40 randomized
  controlled clinical trials, oral and transdermal
  estrogen each reduced the severity of vasomotor
  symptoms, and estrogen was effective in doses
  lower than the usual 0.625 mg of equine estrogens
  or equivalent
• The selective serotonin reuptake inhibitors
  (SSRIs) (venlafaxine and paroxetine) have been
  shown to substantially reduce hot flushes in
  clinical trials
• Progestogens in high daily doses
  (medroxyprogesterone acetate 20 mg per day or
  megestrol acetate 40 mg per day) also reduced
  vasomotor symptoms

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2.2 Symptom Prevention TreatmentVasomotor
Symptoms Hot Flushes Night Sweats

• 2.2.3 Pharmacotherapy
• Veralipride 100 mg per day reduces hot flushes in
  patients treated with GnRH agonists
• Propranolol is no more effective than placebo for
  the reduction of hot flushes whereas evidence for
  clonidines benefit is inconsistent

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2.2 Symptom Prevention TreatmentVasomotor
Symptoms Hot Flushes Night Sweats

• 2.2.4 Complementary and Alternative Therapies
• Phytoestrogens have not been shown in most
  clinical trials to decrease vasomotor symptoms
  significantly better than placebo. Different
  results may relate to differences in women (not
  all of them absorb phytoestrogens equally well)
  or differences in the products tested
• Dong quai has been shown in a clinical trial to
  be not more effective than placebo for the
  treatment of hot flushes
• Evening primrose oil (gamma-linolenic acid) is
  not more effective than placebo for the reduction
  of hot flushes

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Unblinding Experiences

• Mother daughter
• Husband wife
• Other clinics
• Our most active participants

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Participant Perceptions

• Detroit Clinic
• Overall (n 321)
• Those who guessed correct study medication 62
• E plus P
• Those who guessed correct study medication 65
• Placebo
• Those who guessed correct study medication 58
• Thought they were on hormones or didnt know
  42
• Take home message not everyone knew what they
  were on!

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Participant Perceptions

• Symptoms since discontinuation

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Gynecologist Principal InvestigatorPoint of
View

• What I tell my patients about WHI
• Its not just another study
• Provide informed consent if I prescribe hormone
  therapy
• How I suggest stopping hormone therapy
• Cold turkey
• Like surgical menopause for many women
• Tapering
• Lowering dose
• Drop a pill a week
• Patches, patches, patches

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