2/14/05njm

Q. My patient is not doing too well with her hormone replacement
therapy. Options?

A. There are many options: pharmacologic, behavioral, dietary, and
cultural.

See below

#1 What are some cross-cultural considerations in menopausal women?

#2 What about Menopausal hot flashes?

#3 What about Treatment of menopausal symptoms in women not taking
systemic

estrogen?

#4 What are the recommendations for estrogen replacement therapy**?**

#1 **What are some cross-cultural considerations in menopausal women?**

Menopause is a biocultural phenomenon and a normal part of the female
life cycle. Cultural, sub-cultural, and individual differences in
symptoms make sensitivity and knowledge about the wide range of
menopausal experiences important for physicians treating older female
patients, particularly those physicians who treat patients in or from
non-Western cultures. Important cultural issues include:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Menopause occurs at an earlier age in
some cultures compared with the United States.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Reporting of menopausal symptoms varies
greatly among cultures.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Menopause is viewed as positive rather
than negative in some cultures; a time of relative freedom, mobility,
and improved social status.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Screening for menopause based upon age
and FSH levels may be more accurate than self-reporting of menopause
when planning preventative healthcare, such as prevention of
osteoporosis and coronary heart disease. (See Cross-cultural
considerations in menopausal women)

You, or better yet the patient herself, can go to this web page and find
many plant and 'natural' sources
<http://families-first.com/hotflash/faq/meds.htm>

There are several other documents on the Indian Health Mature Women web
page

<http://www.ihs.gov/MedicalPrograms/MCH/W/WHmature.asp>

Here is a FAQ posted on the IHS WH website for a related topic: Natural
Hormones

<http://www.ihs.gov/MedicalPrograms/MCH/M/MCHdownloads/NaturalEstrogens.doc>

**#2 What about Menopausal hot flashes?**

Next are some recommendations for one of the most troubling symptoms,
hot flashes. The following recommendations are largely consistent with
those of the 2004 position statement from the North American Menopause
Society (NAMS).

For mild vasomotor symptoms, NAMS recommends lifestyle changes
(including keeping the core body temperature cool and regular exercise),
either alone or combined with nonprescription therapies such as soy
foods, isoflavone supplements (from either soy or [red
clover](http://www.uptodateonline.com/application/topic.asp?file=nat_drug/69787&drug=true)),
[black
cohosh](http://www.uptodateonline.com/application/topic.asp?file=nat_drug/40012&drug=true),
or [vitamin
E](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/280203&drug=true).
However, available clinical trial data are insufficient to support their
efficacy. Furthermore, soy foods, isoflavone supplements and black
cohosh all appear to have potential estrogenic effects on the breast. As
a result, do not recommend them to breast cancer patients or women at
high risk for breast cancer.

The most effective therapy for moderate to severe vasomotor symptoms is
estrogen. Perimenopausal women should be reassured that taking estrogen
(either unopposed or combined with progestin) for the management of
menopausal symptoms is a safe therapeutic intervention for the majority
of women.

In the past, short-term therapy (with a goal of symptom management) was
defined as less than five years. However, this definition is somewhat
arbitrary as there is no general consensus about the duration of
short-term vs long-term therapy. In general, use of estrogen therapy
should be used for shortest duration possible, taking into account
symptoms (hot flushes, sleep, sexual function), patient age, and quality
of life.

For women with breast cancer or other contraindications to estrogen use,
there are a number of non-estrogen alternatives that are effective.
Consider the SSRI class of drugs as the first choice. The agent best
studied is venlaxafine, a serotonin and
[norepinephrine](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/183453&drug=true)
reuptake inhibitor, administered at a dose of 75 mg daily.
[Fluoxetine](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/109136&drug=true),
[paroxetine](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/192110&drug=true),
and
[sertraline](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/228347&drug=true)
have also been used successfully.
[Gabapentin](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/113590&drug=true)
(300 to 900 mg/day) is another option.

For those with hypertension, transdermal
[clonidine](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/62879&drug=true)
can be tried, although side effects tend to limit its use. Another
option is [megestrol
acetate](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/155292&drug=true),
40 to 80 mg/day. The dose can be gradually decreased once symptoms are
controlled. Hot flashes usually subside after the first week and weight
gain is the most common side effect thereafter. (See Menopausal hot
flashes)

#3 **What about Treatment of menopausal symptoms in women not taking
systemic estrogen?**

Postmenopausal women who have prominent symptoms of vaginal atrophy
and/or vasomotor instability should consider taking estrogen (for the
shortest duration possible depending upon symptoms) unless they have
specific contraindications to estrogen therapy. Consider estrogen for
women who have osteoporosis and who cannot tolerate the treatments
described below. In the absence of these indications, follow-up without
estrogen replacement is appropriate.

**Osteoporosis** --- Treatment for osteoporosis should be based on a
combination of bone mineral density (especially a T score \< -2.5),
clinical manifestations (especially nontraumatic fracture), and age
(especially \>60 years). Consider
[alendronate](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/9677&drug=true)
or
[risedronate](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/73920&drug=true)
as the first choice; the usual dose is 70 mg once per week of
alendronate or 35 mg once per week of risedronate can be used.

[Alendronate](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/9677&drug=true)
and
[risedronate](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/73920&drug=true),
are also effective for prevention of osteoporosis.
[Raloxifene](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/15251&drug=true)
at a dose of 60 mg/day also provides effective prevention but probably
not to the same extent as alendronate. Recommendations for screening for
osteoporosis are discussed separately. All postmenopausal women should
also be encouraged to take both calcium and [vitamin
D](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/38433&drug=true)
supplements, and to exercise on a regular basis.

**Vasomotor instability** --- Most women with severe vasomotor
instability accept estrogen therapy for these symptoms. Thus, use of
other therapies applies predominantly to women with breast cancer.
Consider the SSRI class of drugs as the first choice. The agent best
studied is venlaxafine, a serotonin and
[norepinephrine](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/183453&drug=true)
reuptake inhibitor, administered at a dose of 75 mg daily.
[Fluoxetine](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/109136&drug=true),
[paroxetine](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/192110&drug=true),
and
[sertraline](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/228347&drug=true)
have also been used successfully.
[Gabapentin](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/113590&drug=true)
is another option which may be effective.

For those with hypertension, transdermal
[clonidine](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/62879&drug=true)
can be tried, although side effects tend to limit its use. Another
option is [megestrol
acetate](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/155292&drug=true),
40 to 80 mg/day. The dose can be gradually decreased once symptoms are
controlled. Hot flashes usually subside after the first week and weight
gain is the most common side effect thereafter. Since hot flashes
gradually subside without therapy in most postmenopausal women, any drug
can be gradually tapered after one to two years of administration.

These recommendations are consistent with those of the North American
Menopause Society.

**Urogenital atrophy** --- Consider Replens in conjunction with a
vaginal lubricant initially if symptoms are mild. If these are not
effective, consider low-dose vaginal [conjugated
estrogens](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/220398&drug=true),
a vaginal
[estradiol](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true)
tablet, or the vaginal ring (Estring). For women with more severe
symptoms, some start initially with vaginal conjugated estrogens.

**Cardiovascular disease prevention** --- The best means of primary and
secondary prevention of cardiovascular disease in postmenopausal women
involves attention to risk factors such as smoking, hypertension,
hypercholesterolemia, and diabetes mellitus. (See Treatment of
menopausal symptoms in women not taking systemic estrogen)

#4 **What are the recommendations for estrogen replacement therapy?**

Data from the WHI and the HERS trials have led to changes in the
recommendations for estrogen therapy. These recommendations are
consistent with the Position statement of the North American Menopause
Society.

Continuous estrogen-progestin therapy does not appear to protect against
cardiovascular disease and increases the risk of breast cancer;
unopposed estrogen therapy likewise does not appear to be
cardioprotective, but it does not appear to increase the risk of breast
cancer. In addition, other drugs (eg, bisphosphonates,
[raloxifene](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/15251&drug=true))
can protect against osteoporosis. As a result, the primary indication
for estrogen (unopposed or combined with progestin) therapy at present
is for control of menopausal symptoms.

The United States Food and Drug Administration now requires adding
labels to all estrogen and estrogen-progestin products warning of the
risk of heart disease, stroke, and cancer.

**Management of menopausal symptoms** --- Estrogen therapy remains the
gold standard for relief of menopausal symptoms, and therefore is a
reasonable option for most postmenopausal women, with the exception of
those with a history of breast cancer, CHD, a previous venous
thromboembolic event or stroke, or those at high risk for these
complications. In otherwise healthy women, the absolute risk of an
adverse event is extremely low:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} It has been estimated that the absolute
risk of an adverse event (CHD event, stroke, venous thromboembolic
event, or breast cancer) in a 50-year old woman taking combined
estrogen-progestin for 1 or 5 years would be 1/1000 and 1/200,
respectively.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} The absolute risk would be estimated to
be twice that for a 60-year old woman, because her baseline risk of a
cardiovascular event or breast cancer is approximately twice that of a
50-year old woman.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Based upon the WHI unopposed estrogen
data, in which overall benefits appeared to be equal to risks, one would
estimate no overall increase in adverse events for most women.

Thus, perimenopausal women should be reassured that taking estrogen
(either unopposed or combined with progestin) for the management of
menopausal symptoms is a safe therapeutic intervention for the majority
of women.

In the past, short-term therapy (with a goal of symptom management) was
defined as less than five years. However, this definition is somewhat
arbitrary as there is no general consensus about the duration of
short-term vs long-term therapy. Use of estrogen therapy should be used
for shortest duration possible, taking into account symptoms (hot
flushes, sleep, sexual function), patient age, and quality of life.

In the WHI, the risk of breast cancer with combined estrogen-progestin
therapy did not increase until the fourth year. However, abnormal
mammograms were more common in the HRT group (the majority of abnormal
mammograms represented requests for additional views). Thus, routine
mammograms and breast exams are essential, even if HRT is used
short-term.

**Adding a progestin** --- Endometrial hyperplasia and cancer can occur
after as little as six months of unopposed estrogen therapy; as a
result, a progestin should be added in women who have not had a
hysterectomy.

Although the overall risk-benefit profile in the WHI for unopposed CEE
appeared more favorable than for combined CEE 0.625 mg with MPA 2.5 mg,
use of lower than standard progestin doses, less frequent administration
(eg. quarterly), alternate routes (progestin IUDs), or lower doses of
estrogen without progestin may not reliably prevent endometrial
hyperplasia and carcinoma. The use of unopposed estrogen is not
recommended, or non-standard progestin regimens in women with an intact
uterus. However, if an alternative progestin regimen is used, close
endometrial surveillance should be performed pending additional data on
non-standard regimens.

Women who have undergone hysterectomy should not receive a progestin.

  **Preparations** --- Both the WHI and HERS trials provided data only
on combined, continuous [conjugated
estrogens](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/220398&drug=true)
(0.625 mg) and [medroxyprogesterone
acetate](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/154223&drug=true)
(MPA 2.5 mg), a synthetic progestin. Estrogen preparations other than
conjugated estrogens, and progestins other than MPA (such as natural
[progesterone](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/212059&drug=true))
should be discussed with the patient. It is important to emphasize that
it is not known if other hormones or regimens (eg, cyclic therapy) are
safer for the breast or cardiovascular system. Conjugated estrogen and
17-beta
[estradiol](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true)
(oral or transdermal) appear to be equally effective for the treatment
of hot flashes.

Although there are epidemiologic data which suggest a lower risk of
venous thromboembolic events with transdermal rather than oral estrogen
preparations, there are no clinical trial data demonstrating a better
cardiovascular risk profile for transdermal preparations.

**Dose** --- Although it is not known if lower doses of estrogen or
progestin have less of an effect on the breast and cardiovascular
system, consider using low dose estrogen when possible (eg, 0.3 mg
[conjugated
estrogens](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/220398&drug=true)
or 0.5 mg
[estradiol](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true)).
In some studies, these doses have been adequate for symptom management
and prevention of bone loss.

 **Vaginal estrogen** --- Vaginal estrogen administration (available as
cream, tablets, or rings) is an extremely effective therapy for
genitourinary symptoms. It is an excellent option for nearly all
postmenopausal women (with the exception of breast cancer patients) and
can be administered long-term as systemic absorption, when appropriate
doses are used, is negligible

**Low-dose oral contraceptives** --- A low-estrogen oral contraceptive
(20 µg of ethinyl
[estradiol](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true))
remains an appropriate treatment for perimenopausal women who seek
relief of menopausal symptoms. Most of these women are between the ages
of 40 and 50 years and are still candidates for oral contraception. For
them, an oral contraceptive pill containing 20 µg of ethinyl estradiol
provides symptomatic relief while providing better bleeding control than
conventional estrogen-progestin therapy because the oral contraceptive
contains higher doses of both estrogen and progestin (which suppresses
the hypothalamic-pituitary-ovarian axis).

In our practice, when women taking a low-dose oral contraceptive during
menopause reach age 50 or 51 years, discuss stopping the pill
altogether, or changing to an estrogen regimen if necessary for
symptoms. If estrogen is then given, the same recommendations for use
would apply (for management of symptoms but not for disease prevention).
Because women at this age are apt to have hot flushes when estrogen is
stopped abruptly, consider tapering the oral contraceptive by one pill
per week as described for estrogen therapy.

**Disease prevention** --- Only the minority of women who are unable to
successfully discontinue estrogen without persistent symptoms should
consider long-term estrogen therapy. Estrogen may also be given for
osteoporosis prevention to selected women who cannot take a
bisphosphonate or
[raloxifene](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/15251&drug=true).
As long as there are no obvious contraindications to estrogen, it can be
considered in these women once the breast cancer and cardiovascular
risks are discussed in detail.

**CHD** --- In the 2001 American Heart Association (AHA) guidelines for
estrogen therapy, long-term therapy was no longer recommended for either
primary or secondary prevention of CHD. This recommendation still
applies based upon the results of the WHI and HERS-II trials, and is
consistent with the Position statement of the North American Menopause
Society.

Although it is possible that other estrogen preparations or doses might
not have the same negative cardiovascular effects as conjugated estrogen
and MPA, it is safest to assume that combined therapy has some
beneficial effects (fracture and colon cancer), but has significant
risks that outweigh the benefits for many women.

**Osteoporosis** --- Although some previously recommended estrogen as a
first-line choice for prevention of osteoporosis, some now recommend
bisphosphonates or
[raloxifene](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/15251&drug=true).

  

**Dementia** --- Given the available WHI data, hormone therapy should
not be initiated after age 65 years to prevent dementia. There is
insufficient evidence to either support or refute that hormone therapy
use in perimenopausal women is effective for the prevention of later
dementia.

**Women with POF** --- Data from the WHI should not be extrapolated to
women with premature ovarian failure (menopause before age 40 years) in
whom hormone therapy is generally initiated at a younger age.

**Women with breast cancer** --- Although women with breast cancer often
experience early menopause due to adjuvant chemotherapy, and may have
vasomotor symptoms due to
[tamoxifen](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/254457&drug=true)
therapy, estrogen therapy should not be prescribed.

In the HABITS trial, 434 women with breast cancer were randomly assigned
to receive two years of HRT (estrogen alone or with progestin depending
upon hysterectomy status) or best treatment without hormones (no placebo
given). After a median follow-up of 2.1 years, 26 women in the hormone
group and seven in the non-hormone group had a new breast cancer event
(relative hazard 3.5; 95 percent CI 1.5 to 8.1). Based upon the
excessive risk in the hormone group, the study was terminated in
December 2003.

**Androgen replacement** --- The known decrease in ovarian androgen
production rates and serum androgen concentrations has caused concern
that menopause might be associated with a decline in libido. An
age-associated decline in sexual desire has been observed in both men
and women. However, it is unclear whether the decline in libido in women
is age- or menopause-related, since studies in women have not shown a
significant correlation between libido and the serum
[estradiol](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true)
or
[testosterone](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/256878&drug=true)
concentration.

Clinical trials of exogenous
[testosterone](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/256878&drug=true)
replacement in women generally have been poorly designed and produced
inconsistent results and there are potential risks. Thus, until the
beneficial effects of androgen replacement are better established, it
cannot be routinely recommended to postmenopausal women, particularly in
light of the WHI study

**Cessation of hormone replacement** --- Many women eventually choose to
discontinue hormone replacement after either short-term or long-term
therapy. The major reason is concern about breast cancer. Abrupt
withdrawal of exogenous estrogen at any age results in return of hot
flashes (often severe). Thus, it is essential to taper therapy (in
particular the estrogen) to avoid recurrence of vasomotor symptoms.
Consider decreasing the estrogen by one pill per week (ie, six pills per
week, then five pills per week, etc) until the taper is completed. The
progestin is tapered on the same schedule.

Some women are unable to tolerate a six-week taper, in which case,
consider tapering over twelve rather than six weeks (ie, six pills per
week for two weeks, five pills per week for two weeks, etc). A small
subset of women (perhaps one in ten) has severe and persistent vasomotor
flushes, or a subjective decline in cognitive function and performance,
even after a slow taper. In these women, alternatives such as
venlaxafine 75 mg/day or
[clonidine](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/62879&drug=true)
can be tried and, if ineffective, estrogen can be resumed if the value
of symptom relief outweighs the potential risks.

The implications of stopping estrogen-progestin therapy include:

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Return of estrogen deficiency symptoms
(hot flashes, but not genitourinary atrophy symptoms, can be minimized
with a taper).

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Resumption of bone loss

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Decrease in breast cancer risk to
baseline after five years

The effect of estrogen cessation on coronary disease is not known but
ERT has been associated with no evidence of benefit for either primary
or secondary prevention and there is some suggestion of harm.

**Other guidelines** --- The United States Preventive Services Task
Force has issued evidence-based guidelines similar to those outlined
here.

In contrast, the International Menopause Society (IMS), which argues
that the results of the WHI are not applicable to women considering
hormone therapy at the time of the menopausal transition, suggests that
estrogen therapy may still be a reasonable strategy for prevention of
osteoporosis and heart disease. However, based upon available data, the
authors of this topic review recommend following the NAMS rather than
the IMS guidelines. **(See Recommendations for estrogen replacement
therapy)**

**Resources**

**Cross-cultural considerations in menopausal women: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/21875&type=A&selectedTitle=16~138>

**Menopausal hot flashes: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/12978&type=A&selectedTitle=23~138>

**Treatment of menopausal symptoms in women not taking systemic
estrogen: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/6969&type=A&selectedTitle=4~138>

**Recommendations for estrogen replacement therapy: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/9609&type=A&selectedTitle=3~138>

**Hormone preparations for estrogen replacement therapy: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/8599&type=A&selectedTitle=2~138>

**Cochrane Library**

Hogervorst, E., Yaffe, K., Richards, M., Huppert, F. Hormone replacement
therapy for cognitive function in postmenopausal women (Cochrane
Review). In: *The Cochrane Library,* Issue 1, 2003. Oxford: Update
Software.

Implications for practice

There is little evidence of benefits of ERT or HRT on overall cognitive
function, although there was improvement on one test of verbal memory, a
test of abstract reasoning and a test of speed and accuracy in surgical
menopausal women of a relatively young age who were treated with 10 mg
intramuscular bolus injections of E2 monthly. Based on available
evidence, ERT or HRT cannot be recommended for overall cognitive
improvement or maintenance.

Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, Wells G,
Tugwell P, Cranney A. Exercise for preventing and treating osteoporosis
in postmenopausal women (Cochrane Review). In: *The Cochrane Library,*
Issue 1, 2003. Oxford: Update Software.

Implications for practice

Aerobics, weight bearing and resistance exercises are all effective on
the BMD of the spine in postmenopausal women. Walking is also effective
on the hip. The results suggest that this may be the best program to
propose to the population, and may be the easiest and simplest program
to implement long-term. There has been no apparent effect seen on
fractures but the authors acknowledge that this is based only on the
results of one high quality study with a two year follow up ([Ebrahim
1997](#stG05@01989909281418293400Ebrahim19971)). The quality of the
reporting of the trials in this meta-analysis was low, in particular in
the area of allocation concealment and blinding.

Norman RJ, Flight IHK, Rees MCP. Oestrogen and progestogen hormone
replacement therapy for peri-menopausal and post-menopausal women:
weight and body fat distribution (Cochrane Review). In: *The Cochrane
Library,* Issue 1, 2003. Oxford: Update Software.

Implications for practice

There is evidence from randomised trials that the use of either
unopposed oestrogen or combined oestrogen/progestogen therapy does not
cause extra weight gain in addition to that normally gained at the time
of menopause. There is evidence from one trial that synthetic oestrogen
does cause extra weight gain compared to non-HRT users, but weight was
not a primary outcome of the trial and there were no controls for
relevant parameters.

Additionally, meta-analysis has found no evidence that the use of HRT
actually prevents the weight gain normally experienced at menopause.
There is insufficient evidence available from randomised studies to be
able to ascertain whether HRT use prevents or at least limits the
menopausal tendency towards redistribution of body fat from a pear shape
to an apple shape. It should be noted, however, that few randomised
trials have specifically addressed the issue of the effect of HRT on
body weight or fat distribution, and trials that have had a different
primary research outcome may not have properly controlled for relevant
parameters such as diet, physical activity and smoking habits.

Gillespie WJ, Avenell A, Henry DA, O\'Connell DL, Robertson J. Vitamin D
and vitamin D analogues for preventing fractures associated with
involutional and post-menopausal osteoporosis (Cochrane Review). In:
*The Cochrane Library,* Issue 1, 2003. Oxford: Update Software.

Implications for practice

As the four large community based trials so far reported each evaluated
a different treatment regimen, an optimal fracture prevention programme
using vitamin D or an analogue cannot yet be confidently recommended. In
the frail elderly (over 80 years of age) in sheltered accommodation, the
administration of vitamin D with calcium co-supplementation appears
effective and may be considered.

Lethaby A, Farquhar C, Sarkis A, Roberts H, Jepson R, Barlow D. Hormone
replacement therapy in postmenopausal women: endometrial hyperplasia and
irregular bleeding (Cochrane Review). In: *The Cochrane Library,* Issue
1, 2003. Oxford: Update Software.

Implications for practice

The evidence that unopposed oestrogen therapy increases the risk of
endometrial hyperplasia is consistently associated with the duration and
strength of dose. Irregular bleeding and consequent treatment adherence
problems may also result.

The addition of oral progestogens administered either cyclically or
continuously for endometrial protection should be considered in women
with an intact uterus. Endometrial hyperplasia may be less likely under
a continuous combined regimen than a sequential regimen, in particular
with long durations of therapy. Regular withdrawal bleeding is expected
with a sequential regimen of O + P but women appear to experience less
irregular bleeding than with a continuous O + P regimen. Irregular or
unscheduled bleeding in the first year of continuous O + P therapy does
not need investigation but endometrial biopsy and hysteroscopy could be
considered after this time.

In current practice, sequential regimens are often recommended as
initial HRT for perimenopausal women, while women who have not
menstruated for more than 1 year are recommended to commence on
continuous regimens. These results should also be applied in the context
of improvement of menopausal symptoms and also long term benefits of
various regimens of hormone replacement therapy together with other
adverse effects such as breast tenderness, abdominal cramps, weight gain
and mood swings.

In women who cannot tolerate or use progestogens, unopposed oestrogen
therapy can be considered, but follow up should include long term annual
endometrial assessment.

Cranney A, Welch V, Adachi JD, Guyatt G, Krolicki N, Griffith L, Shea B,
Tugwell P, Wells G. Etidronate for treating and preventing
postmenopausal osteoporosis (Cochrane Review). In: *The Cochrane
Library,* Issue 1, 2003. Oxford: Update Software.

Implications for practice

Clinicians and policy makers should consider the results of this
meta-analysis when formulating management strategies for women at risk
of, or suffering from the adverse consequences, of osteoporosis. The
results of this meta-analysis have demonstrated that while etidronate
increases bone density and decreases vertebral fractures, its effect on
non-vertebral and hip fractures is uncertain.