HORMONE REPLACEMENT THERAPY (HRT) Evidence-based Guidelines

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HORMONE REPLACEMENT THERAPY (HRT)
Evidence-based Guidelines
7th International Annual Congress Alexandria
12- 2002
Dr Mahdy El- Mazzahy Damietta general Hospital
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Introduction

• HRT does not suit everyone.
• Each woman needs to be aware of the benefits and
  potential risks of HRT (pros and cons) so that
  she can make an informed decision.
• Our duty as clinicians is to ensure that women
  are provided with consistent and up-to-date
  information

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HRT and Menopausal Symptoms
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VASOMOTOR HOT FLUSHES includes night sweats

• Grade A
• HRT is an effective treatment for hot flushes
• Tibolone is effective for alleviating the
  severity and reducing the frequency of hot
  flushes
• 
  

N.Z Guidelines May 2001
N.Z Guidelines May 2001
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VASOMOTOR HOT FLUSHES (includes night sweats)

• Grade B
• Unopposed estrogen may be effective for reducing
  the waking episodes that are associated with
  sleep disruption.
• There is no evidence that HRT is effective for
  vasomotor symptoms such as headaches and
  dizziness.

N.Z Guidelines May 2001
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Vaginal atrophy

• Grade A
• Low dose topical estrogen is an effective
  treatment
• E3 (estriol) therapy is also effective but
  requires either the addition of progestogen or
  close monitoring of the endometrium
• Tibolone has been shown to be effective for
  vaginal atrophy
• 
  

N.Z Guidelines May 2001
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PSYCHOLOGICAL SYMPTOMS

• These include depression, mood changes, anxiety,
  irritability, loss of libido, lack of energy and
  memory loss.

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PSYCHOLOGICAL SYMPTOMS

• Grade A
• Estrogen is not an effective treatment in elderly
  women with established Alzheimer's disease
• The addition of low doses of androgens to HRT
  provides relief in women with either a premature
  or surgical menopause who suffer from low libido
  ( for lt2 years).
• 
  

N.Z Guidelines May 2001
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PSYCHOLOGICAL SYMPTOMS

• Grade A
• Tibolone is effective in providing relief from
  low libido in postmenopausal women
• Estrogen replacement therapy is not an effective
  treatment for loss of libido in postmenopausal
  women.

N.Z Guidelines May 2001
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PSYCHOLOGICAL SYMPTOMS

• There is insufficient or inconsistent evidence
  that HRT
• Improves measures of cognition
• 2-Prevents or delays the onset of Alzheimer's
  disease
• 3-Elevates mood or relieves depression

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HRT and risk of cancer
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RISK OF BREAST CANCER

• Continuous combined HRT was associated with an
  increased breast cancer risk if used for four
  years or more
• However this increased risk dissipates quickly
  once use is discontinued.

(NICHD) study November 29,2002. (WHI) July 2002
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RISK OF BREAST CANCER

• Inspite of an increased risk of breast cancer
  diagnosis, the mortality from breast cancer is
  unchanged

. (WHI) July 2002
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RISK OF ENDOMETRIAL CANCER

• Grade A
• Unopposed estrogen therapy should not be used in
  women with a uterus because of an increased risk
  of endometrial cancer.
• Women who have had a hysterectomy may take
  unopposed estrogen therapy

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RISK OF ENDOMETRIAL CANCER

• A
• Combined continuous regimens offer better
  protection of the endometrium than sequential
  regimens.

N.Z Guidelines May 2001
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RISK OF OVARIAN CANCER

• Grade A
• There is no conclusive evidence that combined
  regimens HRT either increases or decreases the
  risk of developing ovarian cancer.

N.Z Guidelines May 2001
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RISK OF OVARIAN CANCER

• Researchers from the National Cancer Institute
  (NCI) have found that women in a large study more
  than 44000 women who used estrogen replacement
  therapy after menopause were at increased risk
  for ovarian cancer.

July 2002 JAMA
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HRT and Osteoporosis
The silent killer
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HRT and Osteoporosis

• Grade A
• HRT and Bisphosphonates has positive effects on
  bone density in postmenopausal women whether or
  not they have osteoporosis
  

N.Z Guidelines May 2001
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HRT and Osteoporosis

• Grade B
• Maintaining HRT use decreases the risk of
  vertebral and non-vertebral fractures in women
  after surgical menopause ,early postmenopausal
  women and in women with established osteoporosis

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HRT and Osteoporosis

• Grade B
• Selective Estrogen Receptor Modulators (SERMs)
  may be useful in the prevention of vertebral
  fractures in women who cannot use HRT
  or bisphosphonates.

N.Z Guidelines May 2001
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ACOG issues New Recommendations On SERMS

• ACOG recommends Raloxifene in the prevention of
  osteoporosis in women at risk for the disease,
  and in the prevention of bone fractures in
  women who already have osteoporosis
• ACOG recommends that SERMS can not be used in
  women with a history of blood clots.
• SERMS increase vaginal dryness and hot flashes.
• 
  
• 
  

ACOG. October,2002
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• HRT and cardiac risk

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HRT and cardiac risk

• Unlike earlier observational studies that
  suggested the possibility of some protection
  against heart disease, recent studies showed a
  small but significant increased risk of non-fatal
  heart attacks

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HRT and cardiac risk

• The Heart and Estrogen Replacement Study (HERS)
  is the first published randomized placebo
  controlled study of HRT in 2763 women with
  established coronary artery disease (HERS I
  1998)
• (HERS II) is follow up study of HERS I the report
  was published in the July 2002 issue of The
  Journal of the American Medical Association
  (JAMA).

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HRT and cardiac risk

• HERS II trial results confirm the initial
  findings of HERS I
• increased risk of coronary events in the early
  years of treatment
• increase in thromboembolic events in the HRT
  group compared with placebo mainly seen in the
  first year of use

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HRT and cardiac risk

• Grade B
• HRT is contraindicated for secondary prevention
  of further coronary disease because of lack of
  documented efficacy and a possible early excess
  mortality.

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the Women's Health Initiative (WHI)study

• This randomized controlled trial examined the
  risks and benefits of long-term combined HRT use
  in 16.608 asymptomatic postmenopausal women
  compared to the placebo group
• The trial has been halted prematurely, after 5.
  years of an 8-year study, due to an increased
  risk of invasive breast cancer.
  .
  

July 2002 JAMA
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The Women's Health Initiative (WHI) Study

• The another WHI trial on estrogen use alone is
  continuing, because of no increased risk for
  breast cancer in this study.
• The report was published in the July, 2002, issue
  of JAMA

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The Women's Health Initiative (WHI) Study

• The key findings after five years / 10,000
  women per year
• Breast cancer increased from 30 to 38 cases ( did
  not appear in the first four years of use).
• Coronary heart disease increased from 30 to 37
  cases (appeared in first year of use )
• Stroke increased from 21 to 29 cases
• (were greatest during the first 2 years )
• Blood Clots increased from16 to 34 cases

July 2002 JAMA
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The Women's Health Initiative (WHI) Study

• The benefits were
• A reduction in colorectal cancer from 16 to 10
  cases
• The reduced risk of colorectal cancer emerged
  after 3 years
• Hip fracture (reduced from 15 to 10)
• 
  

July 2002 JAMA
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New Study of the National Institute of Child
Health and Human Development (NICHD) November 29,
2002

• Unlike the WHI, this study looked at pill and
  patch hormone users as well as several types of
  hormone regimens in 3,823 postmenopausal women

ACOG. November 29,2002
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New Study of the National Institute of Child
Health and Human Development (NICHD)

• Results were consistent with the recent Women's
  Health Initiative
• Continuous combined HRT was associated with an
  increased breast cancer risk if used for five or
  more years.
• no association between breast cancer risk and the
  regimens of either estrogen-alone or sequential
  HRT .
• However, the study found this increased risk
  dissipates quickly once use is discontinued.

ACOG. November 29,2002
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Conclusion

• An Important Note Research Continues,
  Recommendations May Change
• 1-HRT is not recommended for routine use in the
  menopause.
• 2-HRT must be used for as short a time as
  possible with lowest effective dose .

ACOG. August,2002
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Conclusion (cont.)

• 3- The results of the WHI study confirm what is
  already known about the long-term risks of HRT,
  including breast cancer and venous
  thromboembolism.
• 4-HRT has not been proven to be beneficial in
  primary and secondary prevention of coronary
  heart disease in fact may result in a small
  increased rate of CHD.

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Conclusion (cont.)

• 5-ACOG continues to recommend that decisions
  regarding HRT therapy must be made between the
  woman and her physician on an individual basis.
• 6- HRT is the most effective treatment of
  menopausal symptoms .

ACOG. July, 2002
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Conclusion (cont.)

• 7-For patients with osteoporosis, other
  preventive therapies such as bisphosphonates and
  SERM are available. However, for women at risk of
  osteoporosis who also have vasomotor menopausal
  symptoms, HRT can be of benefit .
  .

ACOG. August,2002
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• Thank you