# Presentation: 045157

## Discontinuation of Study Medication: Guidance From the WHI

**Discontinuation of Study Medication: Guidance From the WHI**

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

## How We Informed Participants

- Priority was to our participants
- “First to Know” commitment from the Investigators
- Letters were written by Dr. L’enfant 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.

## http://www.nhlbi.nih.gov/health/prof/heart/other/menopaus/index.htm

- http://www.nhlbi.nih.gov/health/prof/heart/other/menopaus/index.htm

## 2.2 Symptom Prevention & TreatmentVasomotor 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)

## 2.2 Symptom Prevention & TreatmentVasomotor 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

## 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 clonidine’s benefit is inconsistent

- 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 clonidine’s benefit is inconsistent

## 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

- 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

**Notes:**
The one that stands out in my mind is the ppt who called and stated that she thought she may have been one of the reasons why we stopped the study.  She had had 2 heart attacks and 2 strokes, and had been on the active drug in the study.  Also, she had taken HRT through her own physician at some time.  Her outlook was positive.  She was glad she was in the study so that her family would benefit from the increased knowledge about hormones.

"The day she received the message that the E+P study was stopping, a participant at one of the University of Florida Clinics called the clinic manager in tears to say that she could never stop her pills.  She felt so good taking them.  After some supportive comments by the manager, they arranged for her to come to the clinic the following day to discuss her options and find her treatment assignment.  When unblinded, she was found to have been on placebo.  After a stunned silence, she laughed and was able to move on.   Message: not everyone knows what they were taking."

## 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 didn’t know – 42%
- Take home message – not everyone knew what they were on!

## Participant Perceptions

*Symptoms since discontinuation*

## Gynecologist – Principal InvestigatorPoint of View

- What I tell my patients about WHI
- It’s 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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