Welcome to the brave new world of\
what is natural?\
what is synthetic?\
what is a plant source?\
what is a phytoestrogen source?

Many refer to anything from a plant source as a phytoestrogen. Others
only use the term phytoestrogen for items from herbal or food source,
e.g., soy products

The formulary where I work carries 3 main estrogen products\
Premarin: animal source\
Estrace: plant source\
Estraderm: plant source

Use the web site below to sort out what is what on your formulary. This
web site that, while not authoritative, may help you differentiate
between products by source. You might start by scrolling down the page a
bit to the phytoestrogen section.

Meno FAQ: Hot Flash Therapy Guide

<http://families-first.com/hotflash/faq/meds.htm>

Here is an evidence-based resource the sums up the USPSTF
Recommendations for Postmenopausal Hormone Replacement for the Primary
Therapy of Chronic Conditions

<http://www.ahrq.gov/clinic/3rduspstf/hrt/hrtrr.pdf>

Other excellent resources are below.\*

Here is an excerpt from an e-mail discussion from Charles Rhodes,
Endocrinologist at Phoenix Indian Medical Center. The data about HRT is
constantly changing, so please contact him about updates.

At least two distinct issues are being debated here:

Premarin vs. other pharmaceutical estrogens, and prescription drugs vs.
OTC \"nutritional supplements.\"

I\'m not sure we are all speaking the same language. \"Phytoestrogens\"
is a term generally used to describe various plant compounds which can
stimulate estrogen receptors, or which are metabolized to compounds,
which do so.

Some refer to \"vegetable based estrogens.\" Several of the
pharmaceutical estrogen preparations now commercially available in the
U.S. are synthesized from plant-derived substrate. Indeed, Premarin is
the only brand, which I know to be of animal origin; several I don\'t
know.

Some forth two arguments for switching to \"vegetable based estrogen.\"

A.. Price will vary, based on current negotiations, market share, etc.
We depend on\
our pharmacist colleagues to understand the past and present pricing
situation, and\
to forecast the future. Switching formulary drugs can have immense
hidden costs\
when the substitutions are not fully equivalent, as is the case with
estrogens. A\
few extra visits for dosage adjustment can offset what appeared to be a
significant\
savings. Pharmacy must make decisions and recommendations as to when
the\
anticipated saving on acquisition cost will offset the switch-over cost.
In my opinion,\
estrogens are a poor candidate for net savings in this area.
Breakthrough bleeding\
will not just require clinic visits, but will lead to endometrial
biopsies, ultrasound\
studies, and probably some D&Cs.\
B. Vegetable based estrogens are \"more humanely manufactured.\" One\'s
response\
to this would be related to one\'s feelings regarding production of
veal, Frank Perdue\'s\
chickens, mink coats, and puppies. Fake fur is petroleum-based; real fur
is a\
renewable resource. Some things depend on your point of view.

Several people have used the term \"phytoestrogens.\" This covers a huge
spectrum. Phytoestrogens may be regarded as Mother Nature\'s SERMs.
Studied in a low-estrogen setting, they tend to look like estrogen
agonists. Studied in a high-estrogen environment, they tend to look like
antagonists. Results vary, depending on the tissue being studied. In
most cases, the chemical identities of the active ingredients are not
known.

When one substance has been identified (ipriflavone, genistein), there
is no assurance that other substances in the plant being studied do not
have significant effects: estrogenic, antiestrogenic and unrelated.
(Witness the opium poppy, which contains not only morphine and other
endorphin-receptor agonists, but also papaverine.)

Reports of phytoestrogen effects have been widely contradictory. Note
that Hsieh et al. found genistein to enhance growth of
estrogen-responsive malignant cells, and to have estrogen-agonist
effects on normal tissues, while Zava and Duwe found the same
phytoestrogen to have \"potent estrogen agonist and cell-growth
inhibitory actions.\" The latter statement appears self-contradictory
until we recall that for years, estrogen was used to treat breast cancer
in postmenopausal women: some breast cancers are inhibited by
diethylstilbestrol, and presumably they are Estrogen Receptor Positive.
Similarly, there are studies demonstrating that phytoestrogens prevent
and worsen osteoporosis. The \"worsens\" study was done in women who
still had endogenous estrogen, which phytoestrogens can block.

The effects of pharmaceutical estrogen can also vary, depending on the
setting. Many studies attest to estrogen\'s anti-atherogenic effects,
but when women with end-stage atherosclerosis were given estrogen in the
HERS trial, the pro-thrombotic effect of estrogen caused a net worsening
of prognosis in the first year. (The antiatherogenic effect became
dominant in those women who survived the first year.)

I recall one patient who, when switched from Ogen to Premarin,
complained that her breast tenderness was worse (estrogen agonist effect
increased) while her vaginal dryness also worsened (estrogen agonist
effect decreased.) We switched her back. The switch cost her two office
visits\' time and money.

BOTTOM LINE: Estrogen therapy is complex.

**[\*Other resources]{.underline}**

**UpToDate**\
[Hormone replacement
therapy](../index.asp%3Findex=215959&title=Hormone%20replacement%20therapy&order=1~2)
(122 titles)

[http://www.uptodateonline.com/application/index/indexResults.asp?index=215959&title=Hormone%20replacement%20therapy&order=1\~2](http://www.uptodateonline.com/application/index/indexResults.asp?index=215959&title=Hormone replacement therapy&order=1~2)

[Hormone replacement therapy,
Continuous](../index.asp%3Findex=499782&title=Hormone%20replacement%20therapy%2C%20Continuous&order=2~2)

<http://www.uptodateonline.com/application/topic.asp?file=r_endo_f/9755&type=A&selectedTitle=1~1>

**Cochrane Library** (username = Indian, password = health)

<http://www.ihs.gov/MedicalPrograms/CIR/cir-cochrine-library-gateway.asp>

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.