hormone replacement therapy hormone replacement therapy

HORMONE REPLACEMENT THERAPY (HRT) Evidence-based

Guidelines

Dr Mahdy El- Mazzahy Damietta general Hospital

7th International Annual Congress “Alexandria” 12- 2002

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

HRT and Menopausal Symptoms

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 2001N.Z Guidelines May 2001

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

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

PSYCHOLOGICAL SYMPTOMS

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

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 <2 years).

N.Z Guidelines May 2001

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

PSYCHOLOGICAL SYMPTOMS

There is insufficient or inconsistent evidence that HRT

1. Improves measures of cognition

2-Prevents or delays the onset of Alzheimer's disease

3-Elevates mood or relieves depression

HRT and risk of 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

RISK OF BREAST CANCER

RISK OF BREAST CANCERRISK OF BREAST CANCER

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

. (WHI) July 2002

RISK OF ENDOMETRIAL CANCER

Grade AGrade A

• Unopposed estrogen therapy should Unopposed estrogen therapy should not be used in women with a uterus not be used in women with a uterus because of an increased risk of because of an increased risk of endometrial cancer.endometrial cancer.

• Women who have had a hysterectomy Women who have had a hysterectomy may take unopposed estrogen therapymay take unopposed estrogen therapy

RISK OF ENDOMETRIAL CANCER

A

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

• N.Z Guidelines May 2001

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

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

HRT and Osteoporosis

The silent killer

HRT and OsteoporosisGrade A

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

N.Z Guidelines May 2001

HRT and OsteoporosisGrade 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

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

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

•HRT and cardiac risk

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

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).

HRT and cardiac riskHERS 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

HRT and cardiac riskGrade B

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

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

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

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

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

The Women's Health Initiative (WHI) Study

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

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

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

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.

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

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