Download Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for ... PDF

TitleUpdated IMS recommendations on postmenopausal hormone therapy and preventive strategies for ...
LanguageEnglish
File Size240.9 KB
Total Pages19
Document Text Contents
Page 1

Updated IMS recommendations on
postmenopausal hormone therapy and
preventive strategies for midlife health
D. W. Sturdee and A. Pines on behalf of the International Menopause Society Writing Group

Writing Group: D. F. Archer, R. J. Baber, D. Barlow, M. H. Birkhäuser, M. Brincat, L. Cardozo, T. J. de Villiers,
M. Gambacciani, A. A. Gompel, V. W. Henderson, C. Kluft, R. A. Lobo, A. H. MacLennan, J. Marsden, R. E. Nappi,
N. Panay, J. H. Pickar, D. Robinson, J. Simon, R. L. Sitruk-Ware and J. C. Stevenson

INTRODUCTION

The past decade has seen marked fluctuations in opinions

concerning the merits and risks of postmenopausal hormone

replacement therapy (HRT). In July 2002, menopause

management faced a major turning point when the first data

from the Women’s Health Initiative (WHI) trial were released.

This study was categorized as a primary prevention trial for

coronary heart disease. However, the mean age at recruitment

was 63 years, when menopausal symptoms have usually

finished and HRT is rarely started, but this important

difference from common clinical practice was not acknowl-

edged at that time. Instead, WHI investigators concluded that

HRT was not cardioprotective and that its risk–benefit ratio

did not favor the use of postmenopausal hormones for

prevention of chronic diseases. As a result, there was a

dramatic change in prescription habits following recommen-

dations to reserve HRT for very symptomatic women, and to

limit its use to the ‘shortest duration needed’ and to ‘the

lowest effective dosage’. This was the atmosphere in which the

International Menopause Society (IMS) initiated a Workshop

held in Vienna (December 2003) and produced the subsequent

IMS Position Paper resulting from the Workshop discussions.

Basically, the IMS did not accept some interpretations

attributed to the WHI results and, being independent of local

or regional constraints imposed by official health authorities,

called for a more balanced approach to the scientific data.

Because additional information has been accumulated from

both arms of the WHI study, from observational trials and

from other studies during the following years, the first IMS

Statement was updated in 2007, enlarging its scope to

menopause management and adult women’s health in general.

This revised Statement was formulated in a Workshop held in

Budapest in February 2007, in which 30 experts from the

various fields of menopause medicine presented the latest

information and delegates from 60 National and Regional

Menopause Societies from all continents participated in the

discussions.

The 2011 revision of the IMS Recommendations is

published when the atmosphere around the issue of post-

menopausal HRT is much more rational. The pendulum

swung back from its peak negative sentiment following more

detailed data from the WHI study that demonstrated the

importance of the age at initiation and the good safety profile

of HRT in women younger than 60 years. Since these were

exactly the IMS views expressed in the previous Recommen-

dations, the current update is similar in principle to the 2007

version, but with the additional clinical data where needed. It

has been produced by a small Writing Group of experts, and

not from a formal workshop, but is the considered view of the

IMS on the principles of HRT in the peri- and postmenopausal

periods. Throughout the Recommendations, the term HRT

will be used to cover therapies including estrogens, progesto-

gens, combined therapies, androgens and tibolone. The IMS is

aware of the geographical variations related to different

priorities of medical care, different prevalence of diseases, and

country-specific attitudes of the public, the medical commu-

nity and the health authorities toward menopause manage-

ment, different availability and licensing of products, all of

which may impact on HRT. These Recommendations and the

subsequent key messages therefore give a global and simple

overview that serves as a common platform on issues related

to the various aspects of hormone treatment, which could be

easily adapted and modified according to local needs.

GOVERNING PRINCIPLES

Consideration of HRT should be part of an overall strategy

including lifestyle recommendations regarding diet, exercise,

smoking cessation and safe levels of alcohol consumption for

maintaining the health of peri- and postmenopausal women.

Correspondence: Dr D. W. Sturdee, International Menopause Society, PO Box 687, Wray, Lancaster LA2 8LD, UK

CLIMACTERIC 2011;14:302–320

RECOMMENDATIONS
ª 2011 International Menopause Society
DOI: 10.3109/13697137.2011.570590

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Page 2

HRT must be individualized and tailored according to

symptoms and the need for prevention, as well as personal

and family history, results of relevant investigations, the

woman’s preferences and expectations. The risks and benefits

of HRT differ for women during the menopause transition

compared to those for older women.

HRT includes a wide range of hormonal products and

routes of administration, with potentially different risks and

benefits. Thus, the term ‘class effect’ is confusing and

inappropriate. However, evidence regarding differences in

risks and benefits between different products is limited.

Women experiencing a spontaneous or iatrogenic meno-

pause before the age of 45 years and particularly before 40

years are at higher risk for cardiovascular disease and

osteoporosis and may be at increased risk of affective

disorders and dementia. Use of HRT may reduce these risks

but the evidence for this is limited. HRT may reduce

symptoms and preserve bone density and is advised at least

until the average age of menopause.

Counselling should convey the benefits and risks of HRT in

clear and comprehensible terms, e.g. as absolute numbers

rather than, or in addition to, percentage changes from

baseline expressed as a relative risk. This allows a woman and

her physician to make a well-informed decision about HRT.

Written information about risks and benefits as well as

decision aids may be useful.

HRT should not be recommended without a clear indica-

tion for its use, i.e. significant symptoms or physical effects of

estrogen deficiency.

Women taking HRT should have at least an annual consul-

tation to include a physical examination, update of medical

and family history, relevant laboratory and imaging investiga-

tions, a discussion on lifestyle, and strategies to prevent or

reduce chronic disease. There is currently no indication for

increased mammographic or cervical smear screening.

There are no reasons to place mandatory limitations on the

duration of HRT. Whether or not to continue therapy should

be decided at the discretion of the well-informed woman and

her health professional, dependent upon the specific goals and

an objective estimation of ongoing benefits and risks.

Dosage should be titrated to the lowest effective dose.

Lower doses of HRT than have been used previously may

reduce symptoms sufficiently and maintain quality of life for

many women. Long-term data on lower doses regarding

fracture or cancer risks and cardiovascular implications are

still lacking.

In general, progestogen should be added to systemic

estrogen for all women with a uterus to prevent endometrial

hyperplasia and cancer. However, natural progesterone and

some progestogens have specific beneficial effects that could

justify their use besides the expected actions on the

endometrium, e.g. the well-documented blood pressure-

lowering effect of drospirenone. Also, progestogens may not

be alike in regard to potential adverse metabolic effects or

associated breast cancer risk when combined with long-term

estrogen therapy. Low-dose vaginal estrogens, administered

for the relief of urogenital atrophy, are systemically absorbed,

but not at levels that stimulate the endometrium, and so

concurrent progestogen is not required. Direct delivery of

progestogen to the endometrial cavity from the vagina or by

an intrauterine system does provide endometrial protection

and may cause less systemic progestogenic effects than other

routes of administration.

Androgen replacement should be reserved for women

with clinical signs and symptoms of androgen insufficiency.

Androgen replacement often has significant beneficial effects

in women with bilateral oophorectomy or adrenal failure,

particularly on health-related quality of life and sexual function.

BENEFITS OF HRT

General

HRT remains the most effective therapy for vasomotor

symptoms and urogenital atrophy. Other menopause-related

complaints, such as joint and muscle pains, mood swings,

sleep disturbances and sexual dysfunction (including reduced

libido) may improve during HRT. Quality of life and sexual

function may also improve. The administration of individua-

lized HRT (including androgenic preparations when appro-

priate) may improve both sexuality and overall quality of life.

Postmenopausal osteoporosis

HRT is effective in preventing bone loss associated with the

menopause and decreases the incidence of all osteoporosis-

related fractures, including vertebral and hip fractures, even in

women not at high risk of fracture. Based on evidence of

effectiveness, cost and safety, HRT can be considered as one

of the first-line therapies for the prevention and treatment of

osteoporosis in postmenopausal women, younger than

60 years, with an increased risk of fracture. The initiation of

HRT for the sole purpose of the prevention of fractures after

the age of 60 years is not recommended. Continuation of HRT

after the age of 60 years for the sole purpose of the prevention

of fractures should take into account the possible long-term

effects of the specific dose and method of administration of

HRT, compared to other proven non-hormonal therapies.

The protective effect of HRT on bone mineral density

(BMD) declines after cessation of therapy at an unpredictable

rate, although some degree of fracture protection may remain

after cessation of HRT. If the patient is still considered at risk

for fracture after cessation of HRT, additional therapy with

proven bone-sparing medication should be given.

Evidence of the fracture-protective effect of HRT is limited

to standard dosages of conjugated equine estrogen (CEE) and

medroxyprogesterone acetate (MPA), given by the oral route.

Evidence for protection against loss of BMD is available

for lower than standard doses in oral (CEE and 17b-estradiol)
and transdermal (17b-estradiol) administration. Tibolone,
a synthetic molecule that has affinity for the estrogen,

progesterone and androgen receptors, has proven efficacy

Updated IMS recommendations on postmenopausal hormone therapy IMS Writing Group

Climacteric 303

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Page 9

other cognitive functions. During the menopausal transi-

tion, however, some women experience transient prob-

lems, the magnitude of which is usually small.

. Limited evidence from short-term clinical trials in midlife
women suggests that HRT has no substantial cognitive

effect after natural menopause.

. For older women without cognitive impairment, there is
convincing clinical trial evidence that HRT started in the

late postmenopause has no substantial impact on cognitive

abilities.

. For surgically menopausal women, limited evidence from
small clinical trials suggests that estrogen therapy could be

of short-term cognitive benefit when initiated at the time of

oophorectomy.

. The long-term cognitive consequences of HRT initiated
during the menopausal transition or early postmenopause

are unknown. There remains an urgent need for further

research in this area.

Alzheimer’s disease

. For women with dementia due to Alzheimer’s disease,
limited clinical trial evidence indicates that HRT does

not improve dementia symptoms or slow disease

progression.

. Limited clinical trial evidence indicates that HRT
increases all-cause dementia risk when initiated in the

late postmenopause. For women aged 65–79 years, the

excess risk of dementia attributed to hormone use is

about 1.2 per 1000 person-years for estrogen therapy

and 2.3 per 1000 person-years for estrogen plus

progestogen therapy. In this age group, HRT risk may

be higher for women with lower cognitive function at

baseline.

. Observational evidence implies that HRT used by younger
women around the time of menopause is associated with

lower risk of Alzheimer’s disease. Findings from a recent

observational study add new support to the concept of a

therapeutic window, suggesting that using HRT in midlife

only is beneficial, with respect to dementia risk, whereas

starting HRT in later life is harmful. In this study, taking

HRT from midlife onward to older age carried a neutral

effect on dementia risk.

Depression

. The prevalence of depressive symptoms is similar before
and after the menopause. However, depression risk may be

increased during the menopausal transition and the early

postmenopause.

. Limited clinical trial evidence suggests no effects of
estrogen therapy on depression in the late postmenopause.

. Limited clinical trial evidence suggests that short-term
estrogen therapy may benefit depression during the

menopausal transition.

. There is insufficient evidence to recommend HRT, either
alone or as an adjunct, for treatment of depression.

Other neurological disorders

. Potential effects of HRT on the incidence or symptoms of
Parkinson’s disease are largely unknown.

. Based on evidence from a single, small clinical trial,
combined HRT may increase seizure frequency in post-

menopausal women with epilepsy.

. Headache prevalence is lower after menopause than
before. Observational evidence suggests that current

HRT is positively associated with headache.

. Multiple sclerosis symptoms may be influenced by
hormonal status. It is not known whether HRT affects

multiple sclerosis symptoms or progression.

ONCOLOGY

HRT and breast cancer

. The WHI study demonstrated that 7.1 years of treatment
with CEE only did not increase the risk of breast cancer

diagnosis in hysterectomized women. The prospective

cohort in the Nurses’ Health Study also reported that

unopposed estrogen did not increase the risk of breast

cancer diagnosis until after 15 years of estrogen exposure

(mostly CEE). Data about unopposed estradiol are

conflicting, with some studies reporting an increased risk

of diagnosis with short-term duration, but with others

none has been observed.

. Data from the estrogen plus progestogen arm of the WHI
showed an increase in breast cancer diagnosis at an

average follow-up of 5.6 years, although, after adjustment

for confounding variables, this was not statistically

significant. Women who had not used HRT prior to the

study were not at a higher risk for breast cancer diagnosis

for up to 7 years after initiation of therapy.

. Micronized progesterone or dydrogesterone used in
association with oral or percutaneous estradiol may be

associated with a better risk profile for breast cancer than

synthetic progestogens for at least 5 years, but there are

not as yet adequately powered clinical studies.

. The risk of breast cancer diagnosis decreases rapidly after
cessation of HRT; by 5 years, the risk may not be greater

than that in women without any history of exposure.

. Lifestyle factors associated with an increased risk of breast
cancer diagnosis include postmenopausal obesity, in-

creased alcohol intake and reduced physical activity.

. Non-modifiable factors include family history, increased
breast density and atypical ductal hyperplasia.

. The increased risk of diagnosis observed with HRT may be
partially decreased by selecting women with a lower

individual baseline risk and by providing education about

preventive lifestyle measures. One caveat, however, is that

Updated IMS recommendations on postmenopausal hormone therapy IMS Writing Group

310 Climacteric

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Page 10

HRT does not appear to increase the risk of diagnosis in

overweight women whereas it does in women who are not

overweight. This may be due to differences in circulating

estrogen levels related to adiposity.

Endometrial safety, bleeding, HRT
and endometrium

. Unopposed estrogen therapy is associated with a duration-
and dose-related increase in risk of endometrial hyperpla-

sia and cancer.

. This increased risk persists for many years after cessation
of therapy.

. Progestogen prevents the endometrial proliferation of
estrogen.

. Endometrial protection requires an adequate dose and
duration of progestogen.

. Long-term use of sequential combined HRT regimens may
increase the risk of endometrial hyperplasia and cancer,

particularly the long-cycle regimens and where progesto-

gens are used for less than 12 days per 30 days.

. Continuous combined regimens are associated with a
lower risk of endometrial cancer than in the untreated

population.

. In the WHI and Million Women Study, there was no
difference in risk of endometrial cancer with continuous

combined regimens.

. New lower-dose regimens cause less endometrial stimula-
tion and less bleeding.

. Intrauterine delivery of progestogen is a logical route of
administration and provides effective endometrial suppres-

sion, but outpatient insertion may be problematic in

postmenopausal women.

. Data from RCTs on the effect of tibolone on the
endometrium suggest a similar effect to continuous

combined regimens.

. Tamoxifen has an estrogenic effect on the endometrium
whereas raloxifene and other modern SERMs have no

apparent effect.

. Following treatment for endometrial cancer, the use of
HRT is not generally recommended, although there are

few data.

. Obesity increases the risk of developing endometrial
pathology.

HRT and cancers other than breast

Ovarian cancer

. Premenopausal use of the combined oral contraceptive pill
is associated with a reduced risk of developing ovarian

cancer.

. The WHI study is the only RCT to examine HRT and
ovarian cancer risk. In women receiving combined HRT,

there was no significant increase in risk.

. Several case–control and population studies suggest a
significant increase in risk, but the effect of duration or

type of therapy varied among the studies. In one large-

scale trial, the increased risk rapidly returned to normal

within 2 years of cessation, consistent with a promoter

rather than inducer effect.

. In summary, long-term, estrogen-only therapy may be
associated with a small attributable risk of ovarian cancer

of 0.7 per 1000 women per 5 years of use, whilst either a

significantly smaller, or no, increased risk is seen with

combined estrogen plus progestogen therapy.

Lung cancer

. Lung cancer incidence in women continues to increase,
mainly due to smoking, and lung cancer is the largest

contributor to cancer mortality in women.

. Large observational studies have reported a protective
effect of hormonal contraception and postmenopausal

HRT on lung cancer risk.

. In the WHI RCT of estrogen-only therapy, there was no
increase in the risk of non-small cell lung cancer.

. In the WHI RCT of combined estrogen and progest-
ogen therapy, there was an overall non-significant

trend towards an increase in risk of non-small cell lung

cancer.

. An increased risk became significant only in women aged
60–69 years where the absolute attributable risk was 1.8

extra cases of lung cancer per 1000 women taking HRT

for 5 years.

. The risk of death from lung cancer was also higher for
HRT users and this increase was greatest amongst those

who were smokers.

. In women aged 50–59 years, no increased risk of lung
cancer was observed.

Colorectal cancer

. The majority of observational studies show a reduced risk
of colorectal cancer amongst users of oral HRT.

. Three meta-analyses have reported a reduced risk of
colorectal cancer with HRT use with benefit persisting for

4 years after cessation of therapy. A typical effect was

relative risk (RR) 0.80 (95% confidence interval (CI) 0.74–

0.86) for ever-users and 0.66 (95% CI 0.59–0.74) for

current users.

. Results from the WHI randomized trial of estrogen-only
therapy showed no effect of estrogen-only therapy on risk

of colorectal cancer.

. In the WHI RCT of estrogen and progestogen therapy,
colorectal cancer risk was reduced (RR 0.56; 95% CI

0.38–0.81). This effect was predominantly for local

disease and, where spread had occurred, there was more

node involvement and a more advanced stage at diagnosis

amongst users of HRT.

Updated IMS recommendations on postmenopausal hormone therapy IMS Writing Group

Climacteric 311

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Page 18

Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of

hormones and menopausal status with depressed mood in women

with no history of depression. Arch Gen Psychiatry 2006;63:375–82
Ryan J, Burger HG, Szoeke C, et al. A prospective study of the

association between endogenous hormones and depressive symp-

toms in postmenopausal women. Menopause 2009;6:509–17
Bromberger JT, Schott LL, Kravitz HM, et al. Longitudinal change in

reproductive hormones and depressive symptoms across the

menopausal transition: results from the Study of Women’s Health

Across the Nation (SWAN). Arch Gen Psychiatry 2010;67:598–607
Maki PM, Freeman EW, Greendale GA, et al. Summary of the

National Institute on Aging-sponsored conference on depressive

symptoms and cognitive complaints in the menopausal transition.

Menopause 2010;17:815–22

Other neurological disorders

Harden CL, Herzog AG, Nikolov BG, et al. Hormone replacement
therapy in women with epilepsy: a randomized, double-blind,

placebo-controlled study. Epilepsia 2006;47:1447–51
Freeman EW, Sammel MD, Lin H, Gracia CR, Kapoor S. Symptoms

in the menopausal transition: hormone and behavioral correlates.

Obstet Gynecol 2008;111:127–36
MacGregor EA. Estrogen replacement and migraine. Maturitas

2009;63:51–5

Simon KC, Chen H, Gao X, Schwarzschild MA, Ascherio A.

Reproductive factors, exogenous estrogen use, and risk of

Parkinson’s disease. Mov Disord 2009;24:1359–65
El-Etr M, Ghoumari A, Sitruk-Ware R, Schumacher M. Hormonal

influences in multiple sclerosis: new therapeutic benefits for

steroids. Maturitas 2011;68:47–51

Hormones and breast cancer

Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated
equine estrogens on breast cancer and mammography screening in

postmenopausal women with hysterectomy. JAMA 2006;295:1647–57
Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen

therapy and the risk of invasive breast cancer. Arch Intern Med
2006;166:1027–32

Fournier A, Fabre A, Mesrine S, et al. Use of different postmenopausal
hormone therapies and risk of histology- and hormone receptor-

defined invasive breast cancer. Int J Cancer 2008;26:1260–8
Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F.

Estrogen-progestagen menopausal hormone therapy and breast

cancer: does delay from menopause onset to treatment initiation

influence risks? J Clin Oncol 2009;27:5138–3
Kerlikowske K, Cook AJ, Buist DS, et al. Breast cancer risk by breast

density, menopause, and postmenopausal hormone therapy use.

J Clin Oncol 2010;28:3830–7
Chlebowski RT, Anderson GL, Gass M, et al. Estrogen plus progestin

and breast cancer incidence and mortality in postmenopausal
women. JAMA 2010;304:1684–92

Gompel A, Plu-Bureau G. Is the decrease in breast cancer incidence

related to a decrease in postmenopausal hormone therapy? Ann
NY Acad Sci 2010;1205:268–76

Endometrial safety and bleeding

Wiederpass E. Risk of endometrial cancer following estrogen

replacement with and without progestins. J Natl Cancer Inst
1999;91:1131–7

Anderson GL, Judd HL, Kaunitz AM, et al. The effects of estrogen
plus progestin on gynecologic cancers and associated diagnostic

procedures: the Women’s Health Initiative randomized trial.
JAMA 2003;290:1739–48

Lethaby A, Suckling J, Barlow DH, et al. Hormone replacement
therapy in postmenopausal women: endometrial hyperplasia

and irregular bleeding. Cochrane Database Syst Rev 2004;3:
CD000402

Million Women Study Collaborators. Endometrial cancer and

hormone replacement therapy in the Million Women Study.

Lancet 2005;365:1543–51
Langer RD, Landgren B-M, Rymer J, Helmond FA: OPAL investiga-

tors. Effects of tibolone and continuous combined conjugated

equine estrogen/medroxyprogesterone acetate on the endometrium

and vaginal bleeding: results of the OPAL study. Am J Obstet
Gynecol 2006;195:1320–7

Sturdee DW, Archer DF, Rakov V, Lang E, on behalf of the CHOICE

Investigators. Ultra-low-dose continuous combined estradiol and
norethisterone acetate: improved bleeding profile in postmeno-

pausal women. Climacteric 2008;11:63–73
Chin J, Konje JC, Hickey M. Levonorgestrel intrauterine system for

endometrial protection in women with breast cancer on adjuvant
tamoxifen. Cochrane Database Syst Rev 2009;4:CD007245

Bednarek PH, Jenesn JT. Safety, efficacy and patient acceptability of

the contraceptive and non-contraceptive uses of the LNG-IUS. Int
J Women Hlth 2009;1;45–58

Ovarian, lung and other cancers

Grodstein F, Newcomb P, Stampfer M. Postmenopausal hormone

therapy and the risk of colorectal cancer: a review and meta-
analysis. Am J Med 1999;106:574–82

Ritenbaugh C, Stanford J, Wu L, et al. Conjugated equine estrogens
and colorectal cancer incidence and survival: the Women’s Health

Initiative randomized clinical trial. Cancer Epidemiol Biomarkers
Prev 2008;17:2609–18

Marsden J, Sturdee D. Cancer issues. Best Pract Res Clin Obstet
Gynaecol 2009;23:87–107

Morch L, Lokkegaard E, Andreasen A, et al. Hormone therapy and
ovarian cancer. JAMA 2009;302:298–305

Delellis Henderson K, Duan L, Sullivan-Halley J, et al. Meno-
pausal hormone therapy use and risk of invasive colon cancer:
the California Teachers Study. Am J Epidemiol 2010;171:415–
25

Chlebowski R, Anderson G, Manson J, et al. Lung cancer among
postmenopausal women treated with estrogen alone in the
Women’s Health Initiative randomized trial. J Natl Cancer Inst
2010;102:1413–21

Freedman ND, Lacey JV Jr, Hollenbeck AR, et al. The association of
menstrual and reproductive factors with upper gastrointestinal
tract cancers in the NIH-AARP cohort. Cancer 2010;116:1572–81

Attitudes to sexuality in the menopause

Genazzani AR, Gambacciani M, Simoncini T. Menopause and aging,
quality of life and sexuality. IMS Statement following 6th IMS

Workshop, Pisa, December 2006. Climacteric 2007;10:88–96
Hayes RD, Dennerstein L, Bennett CM, et al. Risk factors for female

sexual dysfunction in the general population: exploring factors
associated with low sexual function and sexual distress. J Sex Med
2008;5:1681–93

Nappi RE, Polatti F. The use of estrogen therapy in women’s sexual

function. J Sex Med 2009;6:603–16

Updated IMS recommendations on postmenopausal hormone therapy IMS Writing Group

Climacteric 319

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Page 19

New hormonal products

Pinkerton JV, Utian WH, Constantine GD, Olivier S, Pickar JH. Relief

of vasomotor symptoms with the tissue-selective estrogen complex
containing bazedoxifene/conjugated estrogens: a randomized,

controlled trial. Menopause 2009;16:1116–24
De Villiers TJ. Bazedoxifene: a novel selective estrogen receptor

modulator for postmenopausal osteoporosis. Climacteric
2010;13:210–18

Androgens

Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen

levels in adult females: changes with age, menopause, and
oophorectomy. J Clin Endocrinol Metab 2005;90:3847–53

Warnock JK, Swanson SG, Borel RW, et al. for ESTRATEST Clinical
Study Group. Combined esterified estrogens and methyltestoster-
one versus esterified estrogens alone in the treatment of loss of

sexual interest in surgically menopausal women. Menopause
2005;12:374–84

Burger HG, Papalia M. A clinical update on female androgen
insufficiency – testosterone testing and treatment in women

presenting with low sexual desire. Sexual Health 2006;3:73–78
Davis SR, Moreau M, Kroll R, et al. Testosterone patch for the

treatment of hypoactive sexual desire disorder in naturally
menopausal women: results from the INTIMATE NM1 Study.

Menopause 2006;13:770–9
Hirschberg AL, Rodenberg C, Pack S, et al., for the APHRODITE

Study Team. Testosterone for low libido in postmenopausal

women not taking estrogen. N Engl J Med 2008;359:2005–17
Panay N, Al-Azzawi F, Bouchard C, et al. Testosterone treatment of

HSDD in naturally menopausal women: the ADORE study.
Climacteric 2010;13:121–31

Panjari N, Davis SR. DHEA for postmenopausal women: a review of

the evidence. Maturitas 2010;66:172–9
Nachtigall L, Casson P, Lucas J, et al. Safety and tolerability of

testosterone patch therapy up to 4 years in surgically menopausal

women receiving oral or transdermal estrogen. Gynecol Endocri-
nol 2011;27:39–48

Non-hormonal therapy

Nedrow A, Miller J, Walker M, et al. Complementary and
alternative therapies for the management of menopause-related

symptoms: a systematic evidence review. Arch Intern Med
2006;166:1453–65

Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for
menopausal hot flashes: systematic review and meta-analysis.

JAMA 2006;295:2057–71
Sassarini J, Lumsden MA. Hot flushes: are there effective alternatives

to estrogen? Menopause Int 2010;16:81–8

So-called ‘bioidentical’ or ‘natural’ hormones

Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy:

a review. Menopause 2004;11:356–67

Maclennan AH, Sturdee DW. The ‘bioidentical/bioequivalent’ hor-

mone scam. Climacteric 2006;9:1–3
Fugh-Berman A, Bythrow J. Bioidentical hormones for menopausal

hormone therapy: variation on a theme. J Gen Intern Med
2007;22:1030–4

Sites CK. Bioidentical hormones for menopausal therapy. Womens
Health (London Engl) 2008;4:163–71

Postmenopausal vaginal atrophy

Suckling J, Kennedy R, Lethaby A, Roberts H. Local estrogen therapy

for vaginal atrophy in post menopausal women. Cochrane
Database Syst Rev 2006 Issue 4 CD 001500

Sturdee DW, Panay N, on behalf of the IMS Writing Group.

Recommendations for the management of postmenopausal vaginal

atrophy. Climacteric 2010;13:509–22
Archer DF. Efficacy and tolerability of local estrogen therapy for

urogenital atrophy. Menopause 2010;17:194–203
Ulrich LS, Naessen T, Elia D, Goldstein JA, Eugster-Hausmann M.

VAG-1748 trial investigators. Endometrial safety of ultra-low-
dose Vagifem 10 mg in postmenopausal women with vaginal
atrophy. Climacteric 2010;13:228–37

Labrie F, Archer DF, Bouchard C, et al. Intravaginal dehydroepian-
drosterone (prasterone), a highly efficient treatment of dyspar-
eunia. Climacteric 2011;14:282–8

Influence of methodology and epidemiology
on perception of HRT

Knobe J. Intentional action and side effects in ordinary language.

Analysis 2003;63:190–3
Schwartz LM, Woloshin S. The media matter: a call for

straightforward medical reporting. Ann Intern Med 2004;140:
226–8

Kolata G. Health risk to older women is seen in hormone therapy. The
New York Times, April 4, 2007

Specter M. Denialism: How Irrational Thinking Hinders Scientific
Progress, Harms the Planet, and Threatens Our Lives. London:
Duckworth Overlook Press, 2009

Bluming AZ, Tavris C. Hormone replacement therapy: real concerns
and false alarms. Cancer J 2009;15:93–104

Recent recommendations by other societies

Gompel A, Rozenberg S, Barlow DH; EMAS board members. The

EMAS 2008 update on clinical recommendations on post-
menopausal hormone replacement therapy. Maturitas 2008;
61:227–32

Santen RJ, Allred DC, Ardoin SP, et al. Executive summary:
Postmenopausal hormone therapy: an Endocrine Society scientific
statement. J Clin Endocrinol Metab 2010;95(Suppl 1):s1–66

North American Menopause Society. Estrogen and progestogen use

in postmenopausal women: 2010 position statement of The
North American Menopause Society. Menopause 2010;17:242–
55

Updated IMS recommendations on postmenopausal hormone therapy IMS Writing Group

320 Climacteric

C
li

m
ac

te
ri

c
D

ow
nl

oa
de

d
fr

om
i

nf
or

m
ah

ea
lt

hc
ar

e.
co

m
b

y
Jh

oa
nn

a
M

uk
ai

o
n

07
/2

5/
11

F
or

p
er

so
na

l
us

e
on

ly
.

Similer Documents