# Presentation: 175694

## Wulf H. Utian, MBBCH, PhD
Executive Director
The North American Menopause Society

- Executive Director
- The North American Menopause Society

- National Institutes of HealthScientific WorkshopMenopausal Hormone TherapyBethesda, MarylandOctober 23-24, 2002

## Personal DisclosureWulf H Utian

**	****AS PRESIDENT OF A LARGE CLINICAL RESEARCH CENTER (Rapid Medical Research) :**
**	****●****ADVISORY/CONSULTATION:  Berlex, Eli Lilly, Endeavor, Pfizer, Warner Chilcot**
**	****●****RESEARCH FUNDING: Amylin, 3M, Barr, Berlex, BMS, Lilly, Endeavor, Forest, Neurocrine Biosciences, Novartis, Novo Nordisk, Organon, Pharmacia, P & G, Pfizer, Roche, Sepracor, Solvay, Wyeth, Yamanouchi**
**	****Consultant Gynecologist, The Cleveland Clinic**
**	****Professor Emeritus, Case Western Reserve University**

## The nonprofit scientific organization

- dedicated to promoting women’s health
- at midlife and beyond through an understanding of menopause

## NAMS

- Unique multidisciplinary membership
- Convenes world’s leading annual scientific meeting on menopause
- NAMS’s official scientific journal *Menopause* ranked #1                     out of 52 Ob/Gyn journals by Science Citation Index

## NAMS

- Award winning Web site attracts  >250,00O visitors weekly
- Consumer and professional education materials
- The preeminent resource on menopause for healthcare professionals, the media, and      the general public

## “Most of the time 
in our world 
truth is just opinion.”

                  Michael Ondaatje, Anil’s Ghost.

- in our world
- truth is just opinion.”
-                   Michael Ondaatje, *Anil’s Ghost.*

## NAMS actions

- NAMS HT Advisory    Panel report
- NAMS Gallup Survey       on HT and Quality of Life, and response to the WHI EPT-arm termination

## Report from NAMS advisory panel on postmenopausal hormone therapy

-  Amended and revised October 6, 2002

## Population studied in HERS and WHI

- Majority of participants were randomized              at least 10 years after menopause
- Neither trial evaluated:
- Perimenopausal women
- Women with early menopause (40-50 yrs)
- Women with premature menopause (<40 yrs)
- Panel therefore considered all                      published evidence

## Findings from HERS and WHI

- Non significant breast cancer risk directly related to duration  of therapy
- Significant risk for coronary heart disease (CHD) and venous thromboembolism observed during first year of therapy
- CHD risk not significantly elevated in    following years

## Conclusions from HERS and WHI

- Absolute risks of CCEPT will be higher in:
- women at risk for CHD, stroke, or thromboembolism
- older women
- For older women, absolute benefits may          be higher as well (osteoporosis and colon cancer more prevalent)
- Absolute risks and benefits will be lower         in younger postmenopausal women (CHD, stroke, and osteoporotic fracture less common)

## Basic recommendations   for clinical practice: agreement among panelists

- The treatment of menopause symptoms                   (eg, vasomotor and urogenital) remains the    primary indication for EPT and ET.
- The only menopause-related indication for      chronic progestogen use appears to be endometrial protection from unopposed estrogen therapy.
- For all women with an intact uterus who are using estrogen therapy, clinicians are advised to prescribe adequate progestogen, whereas women without      a uterus should not be prescribed a progestogen.

## Basic recommendations for clinical practice: agreement among panelists (continued)

- No EPT regimen should be used for primary or secondary prevention of coronary heart disease (CHD).         Proven alternate cardioprotective  regimens should be considered.
- The effect of ET on CHD is not yet clear.  Until confirming data are available,          ET should not be used for primary or secondary prevention of CHD.

## Basic recommendations for clinical practice: agreement among panelists (continued)

- Many EPT and ET products are FDA-approved for the prevention of postmenopausal osteoporosis.
- However, because of the potential risks associated with these forms of therapy, alternatives should also be considered, weighing the risks and benefits of each.
- WHI and HERS data cannot be directly extrapolated to symptomatic perimenopausal women or women experiencing                           early menopause (40 to 50 years of age)              or premature menopause (<40 years).

## Basic recommendations for clinical practice: agreement among panelists (continued)

- Use of EPT or ET should be limited       to the shortest duration consistent with treatment goals, benefits, and risks for the individual woman, taking into account issues of quality of life.
- Lower-than-standard doses of EPT    and ET should be considered.

## Basic recommendations for clinical practice: agreement among panelists (continued)

- Alternate routes of administration of EPT  may offer advantages, but the long-term benefit-risk ratio has not been demonstrated.
- An individual risk profile is essential  for  every woman contemplating any regimen     of EPT or ET.
- Women should be informed of known risks.

## Basic recommendations for clinical practice:                      no consensus among panelists

- What are current acceptable definitions of short-term and long-term hormone therapy?
- How long should hormone therapy be prescribed for symptom relief?
- Do reasons exist for extended hormone therapy?

## Basic recommendations for clinical practice: no consensus among panelists(continued)

- Does either premature menopause or premature ovarian failure represent an indication for preventive EPT or ET?
- Is there a consensus on how best to discontinue hormone therapy?
- Is it possible to make general conclusions about all members of the estrogen and progestogen families?

## Immediate needs for future research

- Time precludes oral presentation.
- Listed in the handouts provided.

## Immediate needs for future research

- Beyond symptoms, are there biologic differences between symptomatic and asymptomatic women that affect the benefit-risk profile?
- Do different estrogens and progestogens, different doses, and different routes of administration have the same benefit-risk profiles as the hormones used in HERS and WHI?
- Are the benefits and risks of ET substantially different from EPT?  Is progestogen responsible  for the negative effects of EPT?

## Immediate needs for future research (continued)

- Is continuous progestin, as opposed to sequential progestin, responsible for adverse cardiovascular and breast effects?
- What is the effect of different progestogens on breast cancer risk?
- Is the endogenous level of estradiol and/or  estrone a significant modifier of risk and/or benefit?
- Do women experiencing early or premature menopause  and highly symptomatic perimenopausal women have the same benefit-risk profiles as the women studied in the WHI?

## Immediate needs for future research (continued)

- Are there genetic or environmental factors that significantly alter the risk-benefit profile for EPT/ET?
- How are quality of life issues factored into the risk-benefit profile for EPT/ET?
- What is the role of ET in the primary prevention of CHD?
- Can women at risk for deep vein thrombosis and pulmonary embolism be identified?
- What are the long-term effects of EPT/ET on dementia and Alzheimer’s disease?

## NAMS Gallup survey

- Examined the effects of HT on    quality of life (QOL) in a random sample of symptomatic and asymptomatic postmenopausal  women in the United States.
- Utilized Utian Quality of Life Scale (UQOL) and Greene Climacteric Scale.

## Sample description

- 600 women >1 year postmenopause with intact uterus
-  196 on HT
-  404 not on HT
- Mean age 57.1 years
-  SD 4.07
-  Range 50-65

## Current vasomotor symptoms

- *P<0.01; ** P<0.001

- 38%

- 13%

- 28.0%

- 11%

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

- 40

- Percent (%)

- Hot flashes

- Night sweats

- Not on HT

- On HT

- **

- *

## Rated Satisfaction with HT

**13.8%**

**35%**

**51.2%**

**0**

**20**

**40**

**60**

**Percent (%)**

**No or Slight**

**Moderate**

**Much or Very Much**

**Improvement**

- Improvement Scale  (1-5)
- No Improvement (1) to Very Much Improved (5)

## Vasomotor symptomsconclusions

- HT significantly reduces symptoms associated with menopause

## Climacteric Symptoms   and QOL

**26.2**

**28.7**

**22.0**

**27.6**

**25.6**

**22.8**

**12.1**

**9.8**

**82.6**

**89.5**

**0**

**10**

**20**

**30**

**40**

**50**

**60**

**70**

**80**

**90**

**UQOL Score**

**Occupational**

**Health**

**Emotional**

**Sexual**

**Total**

**UQOL Domain**

**Hot flashes**

**No hot flashes**

********P*****<0.01**

- *

- *

- *

- *

- *

## Menopause symptoms   and QOL

- 25.3

- 29.4

- 24.2

- 25.6

- 24.2

- 24.3

- 10.4

- 11.6

- 84.1

- 90.9

- 0

- 20

- 40

- 60

- 80

- 100

- UQOL Score

- Occupational

- Health

- Emotional

- Sexual

- Total

- UQOL Domain

- Night sweats

- No night sweats

- *

- *

- **P*<0.01

## Menopause symptoms and QOL: conclusion

- Having menopause symptoms is associated with poorer quality of life.

## Effect of HT on QOL

- 115

## Effect of HT on QOL:conclusion

- HT maintains QOL enjoyed by non-symptomatic postmenopausal women

## Participants pre/post WHI news

- Pre WHI
-    n = 267
- Post WHI
-    n = 334

## Have you heard the news of WHI discontinuation?

- Groups did not differ on proportion of women taking HT or on length of time they had been taking HT.

- 77%

- 17%

- 0

- 20

- 40

- 60

- 80

- Percent (%)

- Yes

- No

## Effects of publicity regarding discontinuation of WHI EPT-arm

- 90.5

- 79.0

- 83.0

- 107.0

- 90.0

- 84.7

- 85.6

- 81.5

- 94.6

- 89.6

- 0

- 20

- 40

- 60

- 80

- 100

- 115

- UQOL total score

- 6-12 months

- 1-2 years

- 2-5 years

- 5-10 years

- >10 years

- HT duration

- P<0.01

- Pre-WHI

- Aware of WHI

## Gallup Survey Conclusions:  HT and Quality of Life 

- HT reduces severity of the vasomotor symptoms associated with menopause
- Having menopausal symptoms is associated with poorer quality of life
- HT maintains QOL enjoyed by non-symptomatic women

## Gallup survey conclusions: effects of WHI publicity 

- An overwhelming proportion of respondents heard about the WHI study cessation.
- Compared to women prior to the WHI announcement, women on HT who were  aware of the WHI announcement:
- were more likely to report menopause symptoms.
- were more likely to experience lower QOL   unless they had been on HT between 1-2 yrs.

## Conclusions and observations

- Estrogens and progestogens remain an essential component of menopause-related pharmacotherapy.
- Further research to answer key questions should be encouraged and funded.
- The WHI data cannot be directly    extrapolated to women with                premature and early menopause, or                to symptomatic perimenopausal women.

## Conclusions and observations (continued)

- NIH should release the complete data     of the WHI EPT arm for open scrutiny      and analysis.
- The manner in which NIH announced   the trial results was poorly planned and executed, resulting in unnecessary upset for millions of women.

## NIH must develop a mechanism for announcement of critical research that incorporates clinical implications and recommendations.
This meeting is three months too late! 

- This meeting is three months too late!

- Conclusions and observations (continued)

## Finally...

- 	“While the merits and demerits of the data and the wisdom of the decision   to terminate this arm of the WHI study will be debated for years, the manner  in which the study was terminated was poorly planned, abrupt, and inhumane.”
- 		     	Utian. *Menopause Management, July * 2002.

## www.menopause.org

## Complete report available on         NAMS Web site: www.menopause.org

- Complete report available on         NAMS Web site: www.menopause.org
- NAMS will update recommendations     as more findings become available.