Bioidentical Hormone Therapy
Julia A. Files, MD; Marcia G. Ko, MD; and Sandhya Pruthi, MD
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The change in hormonal milieu associated with perimenopause
ue HT or to seek a safer alternative to FDA-approved HT for
and menopause can lead to a variety of symptoms that can af-
treatment of menopausal symptoms. As a result of the WHI,
fect a woman’s quality of life. Postmenopausal hormone therapy
(HT) is an effective, well-tolerated treatment for these symp-
many women ask their physicians for non–FDA-approved
toms. However, combined HT consisting of conjugated equine
compounded bioidentical HT (CBHT), which is also known
estrogen and medroxyprogesterone acetate has been associated
as OBUVSBM)5, believing that it is safer than FDA-approved
with an increased number of health risks when compared with
conjugated equine estrogen alone or placebo. As a result, some
therapy.3,4 It is estimated that CBHT is a multibillion-dollar
women are turning to alternative hormonal formulations known
industry, possibly affecting millions of women.5
as compounded bioidentical HT because they perceive them
to be a safer alternative. This article defines compounded bio-
identical HT and explores the similarities and differences between
it and US Food and Drug Administration–approved HT. We will
examine the major claims made by proponents of compounded
The findings of the E+P arm (CEE and MPA) of the WHI
bioidentical HT and recommend strategies for management of
patients who request bioidentical HT from physicians.
that were published in 2002 dramatically changed the prescribing practices of physicians in the United States.6
Before the trial demonstrated adverse cardiovascular dis-ease events and a 26% increased risk of breast cancer in female participants, the number of women for whom
BHT = bioidentical HT; bi-est = bi-estrogen; CBHT = compounded
bioidentical HT; CEE = conjugated equine estrogen; E+P = estrogen
E+P was prescribed had been steadily increasing, from
plus progestin; FDA = US Food and Drug Administration; HT = hormone
58 million in 1995 to 90 million in 1999.6 From 1999 to
therapy; MPA = medroxyprogesterone acetate; tri-est = tri-estrogen;
2002, the numbers stabilized; however, within 3 months of publication of the WHI findings, prescriptions for E+P decreased by 63%. Many women stopped HT and some
sought out alternative therapies for treatment of symp-
enopause, the permanent cessation of menstruation
toms associated with menopause.6 In addition to their ef-
that results from loss of ovarian function, can occur
fect on physician-prescribing patterns, the WHI findings
naturally, surgically, or as the result of medical intervention.1
changed the perceptions of patients about the trustwor-
The change in hormonal milieu associated with perimeno-
thiness of the advice dispensed by physicians. A small
pause and menopause can lead to a wide variety of symptoms
survey of 97 women conducted in 2005 demonstrated that
that may negatively affect a woman’s quality of life. The
all the participants had heard of the WHI; a substantial
most common symptoms include hot flashes, night sweats,
number expressed a loss of trust in the information about
emotional lability, poor concentration, and sleep disturbance;
HT that they received from their physicians.7
these can range from mild to severe. Postmenopausal hor-
This sequence of events, combined with celebrity en-
mone therapy (HT) is an effective, well-tolerated treatment
dorsements, media coverage, and the growing number of
for menopausal symptoms. In the United States, a number
women who discontinued HT and experienced a return of
of US Food and Drug Administration (FDA)–approved hor-mone preparations are available for treatment of women with menopausal symptoms.2 In 2002, results from the estrogen
From the Division of Women’s Health Internal Medicine (J.A.F., M.G.K.), Mayo
Clinic, Scottsdale, AZ; and Division of General Internal Medicine (S.P.), Mayo
plus progestin (E+P) arm of the Women’s Health Initiative
(WHI) revealed an increased risk of breast cancer, cardiovas-
An earlier version of this article appeared Online First.
cular disease, stroke, and thromboembolic events in women
Address reprint requests and correspondence to Julia A. Files, MD, Division of
taking conjugated equine estrogen (CEE) and medroxypro-
Women’s Health Internal Medicine, Mayo Clinic, 13400 E. Shea Blvd, Scotts-
gesterone acetate (MPA) compared with those in the placebo
dale, AZ 85259 ([email protected]).
group.3 These findings prompted many women to discontin-
2011 Mayo Foundation for Medical Education and Research .BZP$MJO1SPDr+VMZ
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menopausal symptoms, coalesced to set the stage for the
gen derived from plant sources (17β-estradiol) is available
growth and expansion of the CBHT industry worldwide.
in pills, patches, sprays, creams, gels, and vaginal tablets.
Our research on resources available to patients yielded
These preparations differ from custom CBHT preparations
more than 70 books listed on Amazon.com, numerous
in that they are carefully controlled and regulated formula-
blogs and Web sites, online pharmacies, and an Internet
tions (eg, oral, transdermal, and vaginal preparations), they
company endorsing affiliated physicians as experts in the
are manufactured under strict standards, and their effects
are subjected to scientific scrutiny.13 Numerous peer-re-viewed publications have documented the beneficial effects of various doses of FDA-approved estrogen products on
vasomotor symptoms, hot flashes, bone density, urogenital
The human steroid hormones are divided into the following
atrophy, and fracture prevention.14 In contrast, large-scale,
5 major classes: estrogens, progestogens, androgens, miner-
randomized, controlled studies have not been conducted
alocorticoids, and glucocorticoids. The most common ste-
roid hormones prescribed for the treatment of menopausal
Progesterone bioidentical to that found in humans is
symptoms are the estrogens and progestogens. Estrogens
currently available in certain FDA-approved preparations
and progestogens are available in a wide variety of FDA-
(as oral micronized progesterone in oil or as vaginal pro-
approved and non–FDA-approved formulations for the treat-
ment of perimenopausal and menopausal symptoms.
The term $#)5 refers to hormone preparations that (1)
The term CJPJEFOUJDBMIPSNPOF does not have a standard-
have exactly the same chemical and molecular structure as
ized definition and thus often confuses patients and practi-
the estrogens and progesterone produced within the human
tioners. Women who request bioidentical HT (BHT) from
body, (2) are plant derived, and (3) are specifically com-
their physicians may have differing expectations. Depend-
pounded for an individual patient. Custom CBHT is not
ing on the circumstances, it can mean natural (not artifi-
FDA-approved for treatment of menopausal symptoms.16
cial), compounded, plant derived, or chemically identical
The FDA defines compounding as: “the combining or
to the human hormone structure. The Endocrine Society
altering of ingredients by a pharmacist, in response to a
has defined bioidentical hormones as “compounds that
licensed practitioner’s prescription, to produce a drug tai-
have exactly the same chemical and molecular structure
lored to an individual patient’s special medical needs”.12
as hormones that are produced in the human body.”11
The most common compounded hormones include combi-
This broad definition does not address the manufacturing,
nations of the endogenous estrogens (17β-estradiol, estrone,
source, or delivery methods of the products and thus can
estriol) and progesterone. Although testosterone, dehydro-
include non–FDA-approved custom-compounded products
epiandrosterone, and pregnenolone are sometimes added to
as well as FDA-approved formulations.
CBHT preparations, the main components are usually es-trogen and progesterone.15 Custom CBHT is available only
at select pharmacies. Proponents of custom CBHT prepa-
Numerous FDA-approved hormone preparations are avail-
rations claim that they offer improved safety, efficacy, and
able for the treatment of menopausal symptoms. These
tolerability because of the individualization of the formulas,
include those that fulfill the definition of bioidentical and
the source of the hormones, and the routes of delivery.15
those that are clearly not bioidentical. Products can con-tain only estrogen (synthetic conjugated estrogens; natural,
nonhuman conjugated estrogens; or plant-derived bioiden-tical estrogens), only progestogens (synthetic progestin or
ESTROGEN METABOLISM AND ESTROGEN RECEPTORS
bioidentical progesterone), or a combination of estrogen
A basic understanding of sex hormone metabolism is use-
and progestin. Those that contain synthetic conjugated es-
ful when discussing and prescribing HT. The endogenous
trogens, conjugated estrogens (derived from the urine of
estrogens found in humans include 17β-estradiol, estriol,
pregnant mares), or progestins are not bioidentical to the
estrone, and their conjugates.17 The human ovary pro-
duces 17β-estradiol and estrone, whereas estriol is formed through 16α-hydroxylation of estrone and estradiol.1 Be-
fore menopause, the predominant estrogen in circulation
Currently, FDA-approved products containing bioidentical
is 17β-estradiol, which is mainly secreted by the ovaries.
estrogen and progesterone are available. Bioidentical estro-
Estrone is found in highest concentration after menopause
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TABLE 1. FDA-Approved Bioidentical Hormones
Systemic hormone therapy Vaginal hormone therapy for urogenital atrophy
Estring (Pharmacia & Upjohn Company;
FDA = US Food and Drug Administration. Data from$VSS0QJO0CTUFU(ZOFDPM.13
and is converted in adipose tissue from estradiol and ad-
are found in different tissues. In addition, activity is deter-
renal androstenedione.1,18 Estriol is short acting and is the
mined by which type of estrogen binds to and subsequently
least potent endogenous estrogen. It is found in very low
causes a conformational change that produces an estrogen
concentrations (10 pg/mL) in the serum of nonpregnant
effect specific to the site of the receptor and modulated by
women but is produced in high quantity by the placenta
other activating or repressing molecules.1 For example, the
and, unlike estrone, is not converted to estradiol.17
estrogen receptor α is located in the endometrium, breast
The activity of all forms of estrogen is related to their
cancer cells, and the ovary, whereas the β receptor is found
affinity for 1 of the 2 estrogen receptors, α or β, which
in bone, kidney, lung, and endothelial cells, as well as in
.BZP$MJO1SPDr+VMZ
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several other tissues.1 The binding affinity for the recep-
TABLE 2. Common Compounded Bioidentical Hormone
tor is not strictly proportional to the potency of any given
estrogen: 17β-estradiol has the highest affinity for both α
and β receptors; estrone is midrange in affinity but pre-
dominantly binds to estrogen receptor α; and estriol has
the weakest binding affinity for either receptor.17 Hormone
effects are not dependent only on affinity or dose, as evi-
denced by the fact that a similar biological response can
be achieved with low concentrations of estrogens for a
prolonged period or by the short-term presence of high
a Data were compiled from multiple compounded bioidentical hormone
therapy Web sites and pharmacies on the Internet and from Boothby et
al15; however, this summary is not a comprehensive listing of all avail-
The compounded estrogen formulations most frequently
b All preparations are available in oral, transdermal, sublingual, or vaginal
prescribed contain 2 or 3 forms of estrogen that are “identi-
routes of administration, with the exception of progesterone, which is
cal” to those found in humans: estradiol, estrone, and est-
also available as an injectable medication.
riol in varying percentages. Common CBHT preparations are listed in Table 2. Although the compounded drug bi-estrogen (bi-est) is composed primarily (80%) of estriol,
nant female.1 Oral progestogens are used in HT to prevent
17β-estradiol accounts for most of its estrogenic activity.15
the development of endometrial hyperplasia or neoplasia
It is the most physiologically active form of estrogen and
as a result of estrogen administration.20 All progestogens
is the predominant circulating estrogen before menopause,
cause a change from proliferative to secretory histology of
with 80 times the activity of estriol but making up only 10%
the endometrium (that has been primed with estrogen).21
to 20% of the formulation. In addition to 17β-estradiol and
Progesterone is poorly absorbed and is rapidly metabolized,
estriol, the compounded drug tri-estrogen (tri-est) contains
whereas progestins have high oral bioavailability. The de-
estrone (at a ratio of 8:1:1) and is the predominant circu-
velopment of the process of micronization allowed for im-
lating, active form of estrogen in postmenopausal women.
proved absorption of oral progesterone. Micronized proges-
These 2 formulations (bi-est and tri-est) are generally
terone in peanut oil was approved by the FDA in December
available in oral, transdermal, and vaginal preparations.
1998; before then, micronized oral progesterone was avail-
They must be compounded and usually are labeled with
able only in custom compounded products.22
doses in milligrams, which can be misleading to physi-
Different types of synthetic progestins may have differ-
cians with little experience in this arena. For example, a
ing affinities for, and effects on, the progesterone receptor,
typical formulation of bi-est will be labeled as a 2.5-mg
and they may also activate non–progesterone receptor ste-
dose. This does not reflect a single component but rather
the total of the doses in milligrams of estradiol and estriol
Evidence is not yet sufficient to fully support the claim
combined. If a particular formulation of bi-est is composed
that progesterone is safer than synthetic progestins, but 1 ob-
of 80% estriol, then that formulation would contain 2.0 mg
servational study reported a lower risk of breast cancer in pa-
of estriol and 0.5 mg of estradiol.15 Estimating a dose that
tients receiving progesterone than in patients receiving syn-
is bioequivalent to conventional HT is difficult but is cur-
thetic progestins.24 Further study is needed. The only FDA-
rently under investigation in a phase 1 clinical trial.19
approved oral progesterone is micronized in peanut oil.
In summary, the common CBHT formulations contain US Pharmacopeia–grade, plant-derived estrogens and
chemically converted estrogens (as already noted), but they
Before FDA approval of micronized progesterone in pea-
have only a small percentage of the most active estrogen,
nut oil, custom compounded products were the only source
of micronized oral progesterone.22 For patients with pea-nut or other nut allergy, non-FDA–approved custom-com-
PROGESTERONE METABOLISM, PROGESTINS, AND PROGESTERONE
pounded formulations can provide the option to prescribe
oral progesterone micronized in other oils.25 Progesterone
The term QSPHFTUPHFO refers to both progesterone and syn-
preparations can also be custom compounded into topical
thetic compounds that have progestogenic activity similar to
preparations, but these have not been shown to exert ad-
that of progesterone. The human ovaries and adrenal glands
equate activity to protect the endometrium from the effects
are responsible for progesterone production in the nonpreg-
.BZP$MJO1SPDr+VMZ
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The oversight of accredited compounding pharmacies falls to state pharmacy boards, which are to direct the meth-
od of preparation and enforce standards for compounding as
dictated by the US Pharmacopeia. Thus, most compounded
Proponents of CBHT claim that compounded products con-
products do not have scientifically rigorous clinical testing
taining plant-derived hormones that are bioidentical to those
for either safety or efficacy.5,30 A limited FDA survey in
found in the human ovary offer better safety, efficacy, and tol-
2001 analyzed 29 product samples from 12 compounding
erability than noncompounded, FDA-approved HT.23 Unfor-
pharmacies. None of the products failed identity testing;
tunately, these claims have led to confusion among patients,
however, 10 (34%) of the 29 failed 1 or more quality test,
who often look to their physicians for direction. Therefore,
and 9 (90%) of the 10 failing products also failed potency
physicians who care for women seeking relief from meno-
or assay testing. For FDA-approved therapies, the usual
pausal symptoms need to be familiar with the claims made
comparison failure rate is less than 2%.28
about custom CBHT products and the evidence in the medi-
The FDA has been under increasing pressure to take en-
cal literature on their effectiveness or the lack thereof.
forcement action against compounding pharmacies since a
Objective evidence and scientific studies to substantiate
citizens’ petition was filed in October 2005 by Wyeth Phar-
these claims are lacking, and the use of custom CBHT vs
maceuticals (now part of Pfizer, New York, NY), the manu-
FDA-approved HT remains a topic of ongoing debate in
facturer of Prempro (conjugated estrogens/MPA) and other
the lay press, in alternative medicine literature, and in the
HT formulations, in which the company claimed that the
popular media.15 The claim that the safety profile of bioi-
compounding pharmacies producing CBHT often flagrantly
dentical compounds is better than that of FDA-approved
violate the law.5 The petition resulted in a heightened level
HT15 belies the complexities of the topic. Both CBHT and
of concern about claims made by pharmacies that compound
FDA-approved HT are available in various dosages, com-
BHT, and in January 2008, the FDA censured 7 pharmacies
binations, preparations, and routes of delivery that may
involved in the Internet marketing and compounding of
have differing effects on risk to an individual patient.26
BHT by sending them letters of warning for making false
Despite the contention by proponents that CBHT has been
and misleading claims regarding the safety and effective-
found to be safer, more efficacious, or less likely to cause
ness of their advertised bioidentical hormone preparations.5
breast or uterine cancer than FDA-approved HT, no reports
In January 2008, the FDA ruled that pharmacies could not
published in peer-reviewed journals support this claim.14 Ob-
compound drugs containing estriol without first obtaining
servational data suggest that estradiol in combination with
an investigational new drug authorization. Estriol, a weak
progesterone may confer a lower risk of breast cancer than
estrogen common to most CBHT formulations, has not been
that seen with the CEE+MPA combination used in the WHI,
shown to be safe and effective for the uses for which it is be-
but further study is needed to confirm this finding.27
ing prescribed (eg, bone loss). Currently, estriol is not a com-ponent of any FDA-approved drug.31 This action generated
CLAIM 2: COMPOUNDING PROVIDES IMPROVED DELIVERY AND
considerable controversy because estriol is a component of
Compounded medications require a written prescription from a licensed physician. Prescriptions filled in a com-
CLAIM 3: CUSTOM CBHT CONTAINS SAFER INGREDIENTS THAN
pounding pharmacy are prepared, mixed, and assembled
according to the specifications of the prescriber. Com-
The production of US Pharmacopeia ingredients begins
pounding plays an important role in providing drugs to
with the extraction of diosgenin from plants such as soy and
meet the individualized needs of patients that cannot be met
yams.32 A chemical conversion is then required to produce
by a commercially available FDA-approved preparation. It
progesterone, which is the precursor to the estrogens (estradi-
may provide a different strength, dose, or delivery system,
ol, estrone, and estriol) and the androgens (progesterone and
or it may allow a medication that is otherwise poorly tol-
testosterone) that are used to formulate the final compounded
erated to be essentially reformulated and delivered in an
product.32 This derivation and production process is similar
alternative form (eg, capsules, vaginal creams or troches,
to that of many commercially available, FDA-approved BHT
suppositories, nasal sprays, sublingual drops, topical gels,
products for which safety and efficacy data are available.
rapidly dissolving tablets, or transdermal gels).28,29 Com-pounded hormone preparations are not required to undergo
CLAIM 4: SALIVARY TESTING SHOULD BE USED TO PROVIDE
the rigorous safety and efficacy studies required of FDA-
approved HT and can demonstrate wide variation in active
With the publication of the results of the WHI HT trial in
2002, the risks and benefits attributed to a specific formula-
.BZP$MJO1SPDr+VMZ
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tion of estrogen and progestin were defined. The stark con-
unknown whether the increased risk of breast cancer in the
trast between the observational data and the findings of the
E+P arm of the WHI vs the estrogen-only arm was the re-
randomized, controlled clinical trial led to the recommen-
sult of the addition of a progestin, the specific combination
dation that, in addition to advising that women be informed
and dosage of E+P that was used in the trial, or the specific
of the risks and benefits of HT, the lowest possible dose
of hormone(s) should be used to treat symptoms for the
For many clinicians, the preferred progesterone formu-
shortest period (FDA black box change).33 These findings
lation has been Prometrium (Abbott Laboratories, Abbott
were thought to be generalizable to all available hormone
Park, IL), the FDA-approved, micronized formulation of
oral progesterone, because it is identical to endogenous
Proponents of CBHT claim that customized com-
progesterone and has improved bioavailability.38 In an ob-
pounded formulations provide the best means of “tailor-
servational study, a decreased risk of histology- and hor-
ing or personalizing” therapy. They recommend salivary
mone receptor–defined invasive breast cancer was noted
hormone testing to guide therapeutic decisions for the
with use of a combination of micronized progesterone and
determination of dosages. In its recent position statement
estrogen vs the use of synthetic progestogens; however, fur-
on HT, the North American Menopause Society endorsed
ther study is needed to establish long-term safety.26 There is
the use of the clinical end point of symptom relief to
a lack of published studies in peer-reviewed journals about
the safety and efficacy of CBHT in decreasing breast can-
Easily collected, saliva is similar to an ultrafiltrate of
cer risk. Patients need to be well informed about the risks
blood. Proponents of salivary testing suggest that measured
and benefits, and controlled clinical trials are necessary to
hormone levels are reflective of the levels of free or bio-
provide evidence of long-term safety.
available hormones in the serum of any given patient. The science supporting this type of testing for sex hormones
CLAIM 6: COMPOUNDED BHT HAS A BETTER EFFECT ON BONES
has demonstrated poor reproducibility and large collection
and assay variability even for a given individual, depending
Among the claims in favor of CBHT for better bone health
on the time of day, diet, salivary flow, and hormone be-
are the scientifically based observations about the ben-
ing tested.35,36 Further, the idea that salivary hormone levels
efits of estrogen and testosterone in preventing bone loss,
are related to the menopausal symptoms experienced by
as well as the suggestion of progesterone as an agent that
women has no scientific foundation.30 Even with standard
can “assist” in rebuilding lost bone. These claims are an
FDA-approved HT for menopausal women, measurement
extrapolation of data derived from many peer-reviewed
of serum hormone levels can be potentially misleading
studies using standard doses of manufactured estrogen and
because hormone levels do not always predict therapeutic
testosterone that have shown a beneficial effect of estrogen
effect (thus the recommendation to use symptoms as the
in preventing postmenopausal bone loss.39 The WHI is the
clinical end point for dosing).17,34 The FDA has stated that
only randomized, controlled study demonstrating reduced
no scientific evidence supports the use of salivary testing to
hip fracture risk with E+P therapy.40 None of these claims
titrate hormone dosages or monitor hormone levels.31
has been substantiated directly with CBHT or correlated
Individualization in dosing and delivery methods is
with the wide variety of CBHT preparations in use. Al-
also possible with FDA-approved BHT and nonbioidenti-
though credible by inference with the class of therapy (es-
cal HT because many dosages and delivery methods are
trogen, for example), the claims that CBHT prevents bone
loss or rebuilds lost bone have not been proven.
CLAIM 5: COMPOUNDED BHT HAS A LOWER BREAST CANCER
RISK THAN FDA-APPROVED HTObservational studies and the WHI HT trial have estab-
With all the interest in CBHT generated by the popular
lished an association between HT (E+P) and an increased
media, women often turn for definitive information about
risk of breast cancer.3,37 Advocates for CBHT have claimed
CBHT to their primary care physicians, who are expected
that estriol, given its decreased estrogenic activity, is not
to refill existing prescriptions or write new prescriptions for
only safer but also associated with a decreased breast can-
compounded products. We have found that it is important
cer risk. Some sources found on Internet sites go so far as
to acknowledge the use of the bioidentical formulations
to claim that it protects against cancer, yet no controlled tri-
without appearing to be judgmental or dismissive. Many
als substantiate this claim. Moreover, concerns have been
patients are well versed in the topic and have often con-
raised about the continued use of estriol in high doses and
ducted an exhaustive online investigation before they pres-
its potential risk for stimulating breast parenchyma.38 It is
ent with questions. Prescriptions from other physicians for
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compounded formulations should not be refilled unless
7. McIntosh J, Blalock SJ. Effects of media coverage of Women’s Health
the physician is in full agreement about the need for the
Initiative study on attitudes and behavior of women receiving hormone re-placement therapy. "N+)FBMUI4ZTU1IBSN. 2005;62:69-74.
formulations, their dosage, and indication and is familiar
8. BodyLogicMD. http://www.bodylogicmd.com/. Accessed Aug 18,
with the compounded product. An attempt should be un-
2010. 9. Google. Search term: bioidentical hormones. http://www.google.com/.
dertaken to educate the patient about currently available
FDA-approved BHT products (Table 1). Patients are often
10. Amazon.com. http://www.amazon.com/. Accessed Jul 26, 2010.
surprised to learn that FDA-approved products identical to
11. Endocrine Society. Bioidentical hormones: position statement. 2006. http://www.endo-society.org/advocacy/policy/upload/BH_position_Statement
those in the compounded products are available via a num-
_final_10_25_06_w_Header.pdf. Accessed April 6, 2011.
ber of delivery methods. In accordance with the latest rec-
12. US Food and Drug Adminstration (FDA). FDA Web site. Compounded menopausal hormone therapy questions and answers. http://www.fda.gov
ommendations from the North American Menopause Soci-
/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding
ety, the objective of HT in women who have gone through
/ucm183088.htm. Accessed April 6, 2011.
natural menopause should be the relief of symptoms that a
13. Boothby LA, Doering PL. Bioidentical hormone therapy: a panacea that lacks supportive evidence. $VSS0QJO0CTUFU(ZOFDPM. 2008;20:400-407.
woman finds disruptive to her life. The lowest efficacious
14. Santen RJ, Allred DC, Ardoin SP, et al. Postmenopausal hormone
dose should be prescribed, with the goal of using it for the
therapy: an Endocrine Society scientific statement. +$MJO&OEPDSJOPM.FUBC. 2010;95:s1-s66.
shortest period. For women who have undergone an early
15. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy:
surgical menopause, replacement should continue at least
a review. .FOPQBVTF. 2004;11:356-367.
until the average age of menopause (52 years). 16. Iftikhar S, Shuster LT, Johnson RE, et al. Use of bioidentical hormones
for menopausal concerns: cross sectional survey in an academic menopause
mend annual evaluation of all HT in the context of new
center. +8PNFOT)FBMUI. 2011;20:559-565.
data or changes in the patient’s health. 17. Kuhl H. Pharmacology of estrogens and progestogens: influence of dif- ferent routes of administration. $MJNBDUFSJD. 2005;8(suppl 1):3-63. 18. Coelingh Bennink HJ. Are all estrogens the same? .BUVSJUBT. 2004; 47:269-275. 19. ClinicalTrials.gov. A pharmacokinetic evaluation of bioidentical com- pounded estrogen cream and natural progesterone (HRT). History of Changes
No evidence currently suggests that custom CBHT for-
and the ClinicalTrials.gov Archive Site Web site. http://clinicaltrials.gov/ct2
mulations offer clinically relevant benefit over the FDA-
/archive/NCT00864214. Accessed April 6, 2011. 20. Archer DF. The effect of the duration of progestin use on the occurrence
approved products available to treat the symptoms of
of endometrial cancer in postmenopausal women. .FOPQBVTF. 2001;8:245-
menopause. Because of their wide array of formulations,
251. 21. Moyer DL, Felix JC. The effects of progesterone and progestins on en-
dosages, and delivery systems, FDA-approved HT prod-
dometrial proliferation. $POUSBDFQUJPO. 1998;57:399-403.
ucts can be used to individualize therapy and tailor it to
22. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/
meet the needs and expectations of patients desiring relief
progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial [pub-
of menopausal symptoms. Custom CBHT formulations
lished correction appears in +".". 1995;274:1676]. +".". 1995;273:199-
provide practitioners the option to prescribe HT for women
208. 23. Holtorf K. The bioidentical hormone debate: are bioidentical hormones
who cannot tolerate FDA-approved products or the non-
(estradiol, estriol, and progesterone) safer or more efficacious than common-
hormonal ingredients contained in them.31 Practitioners
ly used synthetic versions in hormone replacement therapy? 1PTUHSBE .FE.
should discuss risks and benefits of the proposed therapy
2009;121:73-85. 24. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast can-
with each patient and should prescribe only the products
cer associated with different hormone replacement therapies: results from the
with which they are familiar and experienced.17,34
E3N cohort study. #SFBTU$BODFS3FT5SFBU. 2008;107:103-111. 25. Prometrium [package insert]. Marietta, GA: Solvay Pharmaceuticals, Inc; 2010. 26. Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel- Chapelon F. Use of different postmenopausal hormone therapies and risk of
histology- and hormone receptor-defined invasive breast cancer. +$MJO0ODPM.
1. Speroff L, Glass RH, Kase NG, eds. $MJOJDBM(ZOFDPMPHJD&OEPDSJOPM PHZBOE*OGFSUJMJUZ. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
27. L’Hermite M, Simoncini T, Fuller S, Genazzani AR. Could transdermal
estradiol + progesterone be a safer postmenopausal HRT? A review. .BUVSJUBT.
2. MacLennan A, Lester S, Moore V. Oral oestrogen replacement therapy ver-
sus placebo for hot flushes. $PDISBOF%BUBCBTF4ZTU3FW. 2001;CD002978. 28. ACOG Committee on Gynecologic Practice. ACOG Committee Opinion 3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of
#322: Compounded bioidentical hormones. 0CTUFU (ZOFDPM. 2005;106(5, pt
estrogen plus progestin in healthy postmenopausal women: principal re-
sults from the Women’s Health Initiative randomized controlled trial. +".".
29. Allen LV Jr. Dosage form design and development. $MJO 5IFS. 2008; 4. Stefanick ML. Estrogens and progestins: background and history, trends 30. Cirigliano M. Bioidentical hormone therapy: a review of the evidence. +
in use, and guidelines and regimens approved by the US Food and Drug Ad-
ministration. "N+.FE. 2005;118(suppl 12B):64-73. 31. North American Menopause Society. Estrogen and progestogen use 5. Patsner B. Pharmacy compounding of bioidentical hormone replacement
in postmenopausal women: 2010 position statement of The North American
therapy (BHRT): a proposed new approach to justify FDA regulation of these
Menopause Society. .FOPQBVTF. 2010;17:242-255.
prescription drugs. 'PPE%SVH-BX+. 2008;63:459-491. 32. Taylor M. Unconventional estrogens: estriol, biest, and triest. $MJO0C 6. Hersh AL, Stefanick ML, Stafford RS. National use of postmenopaus- TUFU(ZOFDPM. 2001;44:864-879.
al hormone therapy: annual trends and response to recent evidence. +".".
33. US Food and Drug Administration (FDA). MedWatch the FDA safety
information and adverse event reporting program. Prempro (conjugated es-
.BZP$MJO1SPDr+VMZ
rEPJNDQrXXXNBZPDMJOJDQSPDFFEJOHTDPN
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings
trogens/medroxyprogesterone acetate tablets). http://www.fda.gov/Safety/
2. Which POF of the following hormone therapies
MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153360.htm. Accessed April 6, 2011.
(HTs) is approved by the US Food and Drug
34. North American Menopause Society. Estrogen and progestogen use in
Administration (FDA) for treatment of menopausal
postmenopausal women: 2010 position statement of The North American
Menopause Society. .FOPQBVTF. 2010;17(2):242-255. 35. Davison S. Salivary testing opens a Pandora’s box of issues surrounding
accurate measurement of testosterone in women. .FOPQBVTF. 2009;16:630-
b. Bioidentical and nonbioidentical medications
36. Granger DA, Shirtcliff EA, Booth A, Kivlighan KT, Schwartz EB. The “trouble” with salivary testosterone. 1TZDIPOFVSPFOEPDSJOPMPHZ. 37. Collaborative Group on Hormonal Factors in Breast Cancer. Breast can-
cer and hormone replacement therapy: collaborative reanalysis of data from
3. Which POF of the following CFTU guides HT dosing
51 epidemiological studies of 52,705 women with breast cancer and 108,411
women without breast cancer. -BODFU. 1997;350:1047-1059. 38. Head KA. Estriol: safety and efficacy. "MUFSO.FE3FW. 1998;3:101-113. 39. Khosla S. Update on estrogens and the skeleton. +$MJO&OEPDSJOPM.F UBC. 2010;95:3569-3577. 40. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin
on risk of fracture and bone mineral density: the Women’s Health Initiative
randomized trial. +".". 2003;290:1729-1738.
4. Which POF of the following is required for compounding?
a. The same strength and dosing for all patients
b. Rigorous clinical testing for safety and efficacy
c. A written prescription and a compounding pharmacy
d. Reformulation and delivery systems available only
CME Questions About Bioidentical Hormone Therapy
e. Both salivary and serum hormone testing for per-
1. Which POF of the following estrogens is the predom-
5. Which POF of the following CFTU describes non–FDA-
inant circulating agent before menopause?
This activity was designated for 1 AMA PRA Category 1 Credit(s).™
Because the Concise Review for Clinicians contributions are now a CME activity, the answers to the questions will no longer be published in the print journal. For CME credit and the answers, see the link on our Web site at mayoclinicproceedings.com. .BZP$MJO1SPDr+VMZ
rEPJNDQrXXXNBZPDMJOJDQSPDFFEJOHTDPN
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings
Print Page E-mail Page COMMON MEDICAL IMPAIRMENTS SUMMARY CONDITION UNDERwRITING FACTORS Alcohol: History of Condition: Alcohol abuse, addiction or dependency leading to social, medical, • When did condition begin?and legal issues. Alcoholics have an uncontrollable need for alcohol • Time since stopped drinking?and continue drinking despite adverse social and occupat
Anaesthesia for Cerebral Aneurysm Repair Epidemiology Exact incidence is unclear but probably about 4%. An annual incidence rupture is about 15-20 per Sex : Male to Female 2 : 3 but more males below 40 and more females after. Rupture : 90% < 12mm, 5% 12-15mm, 5% > 15mm. First aneurysm clipped in 1931, Operating microscope first used for clipping in 1960. Aetiology It had been