FW: Postmenopausal Hormones - Therapy for Symptoms Only

[Guest guest]

Hi All, The below seemed to be worth honorable posting since it is a

possible concern to the ladies. CR is a strong determinant of hormones in

any case. " The annual increase in the risk of serious adverse events

associated with postmenopausal hormone therapy is relatively small, but why

should women take any risk? "

Cheers, Al.

The new england journal of medicine early release

May 8, 2003.

perspective

Postmenopausal Hormones —

Therapy for Symptoms Only

Deborah Grady

Over the past two decades,multiple observational

studies have suggested that postmenopausal hor-

mone therapy reduces the risks of osteoporotic frac-

tures and coronary heart disease.On the basis of this

evidence,hormone therapy was often recommend-

ed for women who were at high risk for fractures

and coronary disease.But these recommendations

were based entirely on observational evidence,

which can sometimes be misleading if the groups

being compared have different risk patterns and

lifestyle.In the early-to-mid-1990s,several large,

randomized trials were initiated to provide defini-

tive evidence concerning the risks and benefits of

hormone therapy for the prevention of disease.The

largest of these trials,the Women ’s Health Initia-

tive (WHI),included more than 27,000 older,gen-

erally healthy postmenopausal women;those with

an intact uterus were randomly assigned to receive

estrogen plus progestin or placebo,and those with-

out an intact uterus were randomly assigned to re-

ceive estrogen alone or placebo.The estrogen-plus-

progestin segment was stopped last summer when

results showed that hormone therapy caused small

increases in the risks of coronary events,stroke,pul-

monary embolism,and breast cancer.There were

also small decreases in the risks of hip fracture and

colon cancer,but the overall harm outweighed these

benefits.The investigators examined the net effect

on these six potentially deadly conditions and re-

ported that hormone therapy results in two such

serious adverse events per 1000 women treated for

one year.After five years of treatment,the risk was

one serious adverse event per 100 women treated.

Given that hormone therapy was associated with

decreased risks of colon cancer and hip fracture,

are there women who are at high risk for these con-

ditions who might have a net benefit from treat-

ment with hormones?A woman with a family his-

tory of colon cancer has a risk of the disease that is

approximately twice that of women with no such

family history.According to the rates of disease and

the relative risks found in the WHI,the estimated

harm is lower among such women,but the net ef-

fect is still about 1.4 serious adverse events per 1000

women per year.A woman with osteoporosis (de-

fined by a T score for bone mineral density that is

lower than ¡2.5)has approximately double the risk

of hip fracture,but the net effect of hormone thera-

py is still about 1.5 serious adverse events per 1000

women per year.What about women at very high

risk for hip fracture,such as those who have already

had a vertebral fracture and have low bone mineral

density?Assuming that the risk of hip fracture is in-

creased by about a factor of five among such wom-

en,the decreases in the risks of hip fracture and

colon cancer will just about balance the increased

risks of coronary events,stroke,pulmonary em-

bolism,and breast cancer.Given the availability

of other effective agents,the use of hormone ther-

apy for the treatment or prevention of osteoporo-

sis is not appropriate for most women.

The annual increase in the risk of serious adverse

events associated with postmenopausal hormone

therapy is relatively small,but why should women

take any risk?Until recently,it has been argued that

many women — even older women who do not have

vasomotor or urogenital symptoms — feel better

when they take hormones.This claim has now been

laid to rest by new results from the WHI.In this is-

sue of the Journal,Hays et al.provide clear evidence

that hormone therapy does not result in better qual-

ity of life among older women without menopausal

symptoms.After one year,there was a statistically

significant difference favoring the hormone group

in three of nine measures of quality of life,but these

differences were not clinically important,represent-

ing an improvement of only 1 to 4 percent over base-

line scores.Two previous randomized trials in

women without vasomotor symptoms also found

no improvement in quality of life associated with

postmenopausal hormone therapy.1,2

The WHI also found that hormone therapy had

no effect on measures of depression,insomnia,sex-

ual function,or cognition.Cognitive function was

measured with the Modified Mini –Mental State Ex-

amination.This measure is not very sensitive for de-

tecting subtle beneficial effects,but the findings

make it unlikely that hormone therapy improves

cognition.These negative results are supported by

findings from the Heart and Estrogen/Progestin Re-

placement Study (HERS)among older women with

coronary disease.3 WHI investigators are also con-

ducting an ancillary study,the Women ’s Health Ini-

tiative Memory Study,that will more completely as-

sess cognitive function and dementia during five

years of follow-up.

It is important to note that the WHI was not de-

signed to test the effect of hormone therapy on vas-

omotor or other menopausal symptoms.The ma-

jority of women enrolled in the WHI did not have

menopausal symptoms.Among the 12 percent of

women who did report moderate-to-severe vasomo-

tor symptoms at base line,the symptoms were un-

likely to be very bothersome,since the women were

willing to be randomly assigned to placebo.In this

subgroup,hormone therapy improved vasomotor

symptoms and reduced sleep disturbance.Multiple

other randomized trials among younger women

with hot flashes have shown that systemic estrogen

therapy is highly effective in relieving vasomotor

symptoms,reducing both the severity and the fre-

quency of hot flashes by about 80 percent 4 and

thereby improving the quality of life.5

The benefit of relief of vasomotor symptoms

needs to be balanced against the risks associated

with hormone use.As noted above,among women

in the WHI,there was one serious adverse event for

every 100 women treated for five years.Most women

with vasomotor symptoms require treatment for a

much shorter duration than five years,and therefore

the risk will be smaller.Furthermore,the average

age of women enrolled in the WHI was 63 years.

Most women with vasomotor symptoms are at least

a decade younger than this,and the rates of under-

lying diseases among younger women are lower.

Thus,the absolute risk associated with hormone

therapy will be lower among younger women who

choose to use it for the relief of symptoms.If the

rates of diseases among 50-year-old women are es-

timated to be about half of those reported for older

women in the WHI,the net effect of hormone ther-

apy in this age group will be about one serious ad-

verse event per 1000 women treated for one year

(see Figure).Is this risk worth the relief of vasomo-

tor symptoms provided by hormone therapy?Other

treatments,including megestrol,selective sero-

tonin-reuptake inhibitors and other antidepres-

sants,and clonidine,provide some relief of vaso-

motor symptoms,but systemic hormone therapy

is the most effective treatment.Hot flashes are not

deadly,but they can be very disabling.Some wom-

en may choose to try other remedies or to live with

their symptoms,whereas others will find the re-

lief of symptoms afforded by hormone therapy

worth the risk.

Are there some perimenopausal women who

should be more concerned about adverse effects of

hormone therapy for the treatment of menopausal

symptoms?Since hormone therapy increases the

risk of coronary events,stroke,breast cancer,and

venous thromboembolic events,women at in-

creased risk for these conditions will incur a higher

absolute risk while taking hormones.All women,

but particularly those at higher risk for the adverse

effects of hormone therapy,should consider alter-

native therapies.Women who choose to take es-

trogen should start with a low dose and gradually

increase it until symptoms are adequately con-

trolled.Vasomotor symptoms resolve within sever-

al months in many women and within a few years

in most women,so an attempt should be made at

least every six months to taper the dose of hormones

and to discontinue therapy.

Postmenopausal therapy with estrogen and

progestin results in increased risks of disease,does

not make asymptomatic women feel better,and

does not improve cognition.There is no role for

hormone therapy in the treatment of women with-

out menopausal symptoms.Women with vasomo-

tor symptoms must weigh the risks associated with

treatment against the benefit of symptom relief.

Vasomotor symptoms occur in about two thirds of

women and are very distressing in 10 to 20 percent.

We clearly need to identify new treatments that are

highly effective and safe.

1.Hlatky MA,Boothroyd D,Vittinghoff E,Sharp P,Whooley MA.

Quality-of-life and depressive symptoms in postmenopausal

women after receiving hormone therapy:results from the Heart and

Estrogen/Progestin Replacement Study (HERS)trial.JAMA 2002;

287:591-7.

2.Greendale G,Reboussin B,Hogan P,et al.Symptom relief and

side effects of postmenopausal hormones:results from the Post-

menopausal Estrogen/Progestin Interventions Trial.Obstet

Gynecol 1998;92:982-8.

3.Grady D,Yaffe K,Kristof M,Lin F,s C,Barrett-Connor

E.Effect of postmenopausal hormone therapy on cognitive func-

tion:the Heart and Estrogen/Progestin Replacement Study.Am J Med

2002;113:543-8.

4.MacLennan A,Lester S, V.Oral estrogen replacement

therapy versus placebo for hot flushes:a systematic review.Climac-

teric 2001;4:58-74.

5.Wiklund I,Karlberg J,Mattsson LA.Quality of life of postmeno-

pausal women on a regimen of transdermal estradiol therapy:a dou-

ble-blind placebo-controlled study.Am J Obstet Gynecol 1993;168:

824-30.

Alan Pater, Ph.D.; Faculty of Medicine; Memorial University; St. 's, NL

A1B 3V6 Canada; Tel. No.: (709) 777-6488; Fax No.: (709) 777-7010; email:

apater@...