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Contents lists available at ScienceDirect

Maturitas
journal homepage: www.elsevier.com/locate/maturitas

Mini review

Perspective on prescribing conjugated estrogens/bazedoxifene for

estrogen-deciency symptoms of menopause: A practical guide
Santiago Palacios a , Heather Currie b , Tomi S. Mikkola c , Erika Dragon d
a

Instituto Palacios, Madrid, Spain

NHS Dumfries & Galloway, Dumfries, Scotland, United Kingdom
Helsinki University Central Hospital, Helsinki, Finland
d
Pzer, Global Innovative Pharma, Europe, Paris, France
b
c

a r t i c l e

i n f o

Article history:
Received 30 October 2014
Received in revised form 9 January 2015
Accepted 11 January 2015
Available online xxx
Keywords:
Menopause
Hot ashes
Postmenopausal hormone replacement
therapy
Selective estrogen receptor modulators
(SERMs)
Bazedoxifene
Osteoporosis

a b s t r a c t
Current guidelines recommend that hormone therapy (HT) in postmenopausal women with a uterus
include a progestin to protect against endometrial hyperplasia. However, many concerns relating to HT
use appear to be related to the progestin component, including cardiovascular risk, breast stimulation, and
irregular vaginal bleeding. Conjugated estrogens (CE) combined with the selective estrogen receptor modulator bazedoxifene (BZA) is a new progestin-free HT option for alleviating estrogen deciency symptoms
in postmenopausal women with a uterus for whom treatment with progestin-containing therapy is not
appropriate. Five double-blind, randomized, placebo-controlled, phase 3 studies, known as the Selective
estrogens, Menopause, And Response to Therapy (SMART) trials have investigated the efcacy of CE/BZA
for relieving vasomotor symptoms (VMS), and effect on bone mass, as well as endometrial and breast
safety in postmenopausal women. In a 12-week study, CE 0.45 mg/BZA 20 mg signicantly reduced the
number and severity of hot ushes compared with placebo at weeks 4 and 12. Unlike estrogen-progestin
therapy (EPT), CE 0.45 mg/BZA 20 mg did not increase breast density compared with placebo. In clinical trials up to 2 years, CE/BZA had a favorable tolerability prole, demonstrated by amenorrhea rates
similar to placebo. Vascular disorders including venous thromboembolic events (pulmonary embolism,
retinal vein thrombosis, deep vein thrombosis, and thrombophlebitis) were rare events, occurring in less
than 1 per 1000 patients. CE/BZA was associated with signicantly higher incidences of amenorrhea and
lower incidences of bleeding compared with CE/medroxyprogesterone acetate in 2 comparative trials.
Therefore, CE 0.45 mg/BZA 20 mg provides an effective, well-tolerated, progestin-free alternative to EPT
for postmenopausal women with a uterus.
2015 Elsevier Ireland Ltd. All rights reserved.

Contents
1.
2.
3.
4.
5.
6.
7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Efcacy of CE/BZA in phase 3 clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Safety and tolerability concerns and contraindications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appropriate candidates for CE/BZA therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Practice points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Research agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Corresponding author. Tel.: +34 915780517; fax: +34 914319951.

E-mail address: ipalacios@institutopalacios.com (S. Palacios).
http://dx.doi.org/10.1016/j.maturitas.2015.01.003
0378-5122/ 2015 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Palacios S, et al. Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deciency
symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003

G Model
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Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Hormone therapy (HT) is established as the most effective therapy for vasomotor symptoms (e.g., hot ushes, night sweats) in
women younger than 60 years [1]. The addition of a progestogen
to systemic estrogen (estrogen-progestin therapy [EPT]) is recommended for nonhysterectomized women to prevent endometrial
cancer [2]. Many concerns about HT appear to be related to the
progestin component, as coronary heart disease risk, increased
mammographic breast density, breast cancer risk, breast pain, and
irregular vaginal bleeding occur more frequently with EPT than
with estrogen therapy (ET) [36]. Thus, there is a need for progestinfree treatment options that protect the endometrium, with a
clinically evidenced efcacy and improved tolerability/safety prole.
Conjugated estrogens (CE)/bazedoxifene (BZA) (CE/BZA;
Duavive , Duavee ) is a novel tissue selective estrogen complex
(TSEC) combining estrogens with a selective estrogen receptor
modulator (SERM). The rationale for TSEC development was
that the SERM component would minimize adverse estrogenic
effects on the endometrium and breast, while maintaining the
benecial effects of estrogens on menopausal symptoms [7]. BZA
was specically selected as this SERM because it showed favorable
preclinical effects on the skeleton, vasomotor activity, and lipid
metabolism, as well as mammary and uterine safety [8]. Gene
expression proling of CE in combination with 3 different SERMs
(BZA, raloxifene, and lasoxifene) showed differential patterns of
gene expression, indicating that different SERM/CE combinations
may have distinct clinical activities [9]. Preclinical data have
shown that whereas CE alone stimulates proliferation of MCF-7
and T47D human breast cancer cells and reduces cell apoptosis,
the addition of BZA at an adequate dose level abrogates these
effects [10]. In a separate analysis, BZA was also shown to be a
more potent inhibitor of CE-dependent in vitro breast cancer cell
proliferation than raloxifene and lasoxifene. A phase 3 study of BZA
alone in postmenopausal women with osteoporosis demonstrated
a favorable long-term safety prole in the endometrium, breast,
and reproductive tract over 7 years [11].
2. Efcacy of CE/BZA in phase 3 clinical trials
CE 0.45 mg/BZA 20 mg once daily tablet (Duavive ) was recently
approved in the European Union for treatment of estrogen deciency symptoms in postmenopausal women with a uterus (12
months since last menses) for whom treatment with progestincontaining therapy is not appropriate [12]. CE 0.45 mg/BZA 20 mg
is also approved in the United States (Duavee ) for treatment of
moderate to severe vasomotor symptoms (VMS) associated with
menopause and prevention of postmenopausal osteoporosis [13].
Safety and efcacy of CE/BZA are supported by 5 double-blind,
randomized, placebo- and active-controlled, phase 3 Selective
estrogens, Menopause, And Response to Therapy (SMART) trials
(Table 1) [1420]. In SMART-2, CE 0.45 mg/BZA 20 mg signicantly reduced the mean daily number of moderate to severe hot
ushes by 74% at week 12, and signicantly reduced hot ush
severity during weeks 3 through 12 (p < 0.001 vs placebo) [15]. In
SMART-3, CE 0.45 mg/BZA 20 mg signicantly increased supercial cells, decreased parabasal cells, and reduced vaginal dryness
compared with placebo in postmenopausal women with moderate
to severe symptoms of vulvar-vaginal atrophy (VVA) at baseline;

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however, the most bothersome VVA symptom and vaginal pH were

not statistically signicantly affected versus placebo [16]. In the 1year SMART-5 study, CE 0.45 mg/BZA 20 mg showed an increase of
0.24% from baseline in lumbar spine BMD at month 12 compared
with a decrease of 1.28% for placeboa signicant (p < 0.01) difference of +1.52% [18]. CE/BZA also exhibited benecial effects on
sleep parameters and menopause-related quality of life [18,20,21].

3. Safety and tolerability concerns and contraindications

CE/BZA was well tolerated in the SMART trials; rates of discontinuation due to adverse events were low and similar to placebo
(Fig. 1 [SMART-5]) [1519]. Higher breast density has been shown
to be associated with lower mammographic sensitivity (i.e., ability
to detect cancer at screening) [22]. In the SMART-5 study, mean
mammographic breast density decreased to a comparable extent
from baseline to 1 year with CE/BZA (0.38%) and placebo (0.44%)
while HT (CE/MPA) signicantly (p < 0.001) increased breast density
(+1.60%) from baseline compared with placebo [23]. Similar reductions in breast density were reported for CE/BZA and placebo at
2 years in an ancillary study to SMART-1 [24]. Incidence of breast
cancer was low and similar to placebo during up to 2 years of use in
the SMART trials [23,24]. The incidence of breast pain/tenderness
among women treated with CE/BZA was similar to placebo across
SMART trials [1519] and signicantly lower than with CE/MPA in
SMART-4 and SMART-5 [17,18].
The addition of BZA to CE reduces the risk of endometrial hyperplasia that can occur with estrogen-only use [12]. Through 12- and
24-month follow-up in the SMART trials, there was no increased
risk of endometrial hyperplasia with CE 0.45 mg/BZA 20 mg [14,18].
Incidences of uterine bleeding and spotting were low and similar
to placebo [17,18,25]. In SMART-4 and SMART-5, CE 0.45 mg/BZA
20 mg was associated with a signicantly higher rate of amenorrhea
(Fig. 2 [SMART-5]) and lower incidence of bleeding compared with
CE/MPA [17,18]. In one study, amenorrhea was reported in 97% of
the women who received CE 0.45 mg/BZA 20 mg during months 10
to 12 [12]. As with other HT, abnormal bleeding requires diagnosis before initiating CE/BZA, and any persistent/recurrent bleeding
during treatment warrants investigation to rule out malignancy.
Although CE and BZA individually have been linked to increased
venous thromboembolism (VTE) risk [26,27], there appears to be no
added risk of combining the two. Across all the phase 3 studies, VTE
was a rare event, affecting less than 1 person per 1000 patients [12].
There were few VTEs in the SMART studies (CE 0.45 mg/BZA
20 mg: n = 3; placebo: n = 1; all deep vein thromboses) [1519,28].
Although the rates of myocardial infarction with CE/BZA were
similar to placebo in the SMART trials, effects of CE/BZA (Fig. 2)
on the cardiovascular system require further data collection and
analysis. In nonhuman primates (postmenopausal monkeys) fed a
high-fat, high-cholesterol diet, CE modestly reduced the severity
of atherosclerosis and complicated plaques in the common carotid
artery; the addition of BZA did not signicantly attenuate these
benets [29]. Statistical power to evaluate VTE and cardiovascular risks is limited by the small number of such events and lack
of long-term follow-up data from the SMART trials. If prolonged
immobilization is anticipated following elective surgery, CE/BZA
should be stopped temporarily beginning 4 to 6 weeks before
surgery [12]. Treatment should not be restarted until the woman is
completely mobilized [12].

Please cite this article in press as: Palacios S, et al. Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deciency
symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003

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Table 1
Study designs of the SMART trials.

N (randomized)

SMART-1 [14]

SMART-2 [15]

SMART-3 [16]

SMART-4 [17]

SMART-5 [18]

3544

332

652

1083

1886

Key eligibility criteria

Aged 40 to 75 years

Postmenopausal women with a uterus

Aged 40 to 65 years
Aged 40 to 65 years
Aged 40 to 65 years
1 moderate to severe
7 moderate to severe
daily hot ushes
VVA symptoms
12 weeks
12 weeks
1 year (1-year extension)

Aged 40 to 65 years

Study duration

2 years

Treatments administered
(once-daily oral doses)

CE 0.625 or 0.45 mg
each with BZA 10, 20,
or 40 mg
Raloxifene 60 mg
Placebo

CE 0.45 mg/BZA 20 mg
CE 0.625 mg/BZA 20 mg
Placebo

CE 0.45 mg/BZA 20 mg
CE 0.625 mg/BZA 20 mg
BZA 20 mg
Placebo

CE 0.45 mg/BZA 20 mg
CE 0.625 mg/BZA 20 mg
CE 0.45 mg/MPA 1.5 mg
Placebo

CE 0.45 mg/BZA 20 mg
CE 0.625 mg/BZA 20 mg
BZA 20 mg
CE 0.45 mg/MPA 1.5 mg
Placebo

Primary endpoints

Incidence of
endometrial
hyperplasia

Frequency/severity
of hot ushes

Vaginal maturation
Vaginal pH
Most bothersome
symptom

Incidence of
endometrial
hyperplasia
Bone mineral density

Incidence of
endometrial
hyperplasia
Bone mineral density

Secondary endpoints

Bone mineral density

Bone turnover markers
Frequency/severity of
hot ushes
VVA measures
Sleep
Menopause-specic
quality of life

Sleep
Menopause-specic
quality of life
Breast pain

Individual VVA
symptoms (dryness,
itching/irritation,
dyspareunia)
Sexual function
Satisfaction with
treatment
Menopause-specic
quality of life

Amenorrhea prole
Breast pain

Osteoporosis
parameters
Bleeding
Breast density
Breast tenderness
Sleep
Menopause-specic
quality of life

1 year

SMART, Selective estrogens, Menopause, And Response to Therapy; VVA, vulvar-vaginal atrophy; BZA, bazedoxifene; CE, conjugated estrogens; MPA, medroxyprogesterone
acetate.

CE/BZA had favorable effects on lipid prole in the SMART

trials, signicantly lowering total and low-density lipoprotein
cholesterol, while increasing high-density lipoprotein cholesterol,
compared with placebo [15,16,19]. CE/BZA had minimal effects on
coagulation prole, consisting of small decreases from baseline in
brinogen and plasminogen activator inhibitor type 1 activities,
and small increases in plasminogen activity [19]. In pooled analyses

of the SMART trials, CE/BZA was not associated with increases in

body weight or body mass index compared with placebo [30].
4. Appropriate candidates for CE/BZA therapy
CE/BZA was studied in healthy nonhysterectomized postmenopausal women, on average 53 to 56 years of age

Fig. 1. Summary of selected safety and tolerability parameters in SMART-5 [18]. a Overall p < 0.05.
bazedoxifene; MPA, medroxyprogesterone acetate; TEAE, treatment-emergent adverse event.

Overall p < 0.001. AE, adverse event; CE, conjugated estrogens; BZA,

Please cite this article in press as: Palacios S, et al. Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deciency
symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003

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Fig. 2. Rates of cumulative amenorrhea for cycles 1 to 13 among postmenopausal women taking CE/BZA, BZA, CE/MPA, or placebo in SMART-5. Reprinted with permission
from endocrine society [18]. a P < 0.001 vs all other treatment groups.
CE, conjugated estrogens; BZA, bazedoxifene; MPA, medroxyprogesterone acetate.

Table 2
Characteristics of women enrolled in the SMART trials [1418,20].
Characteristic
Age
BMI
Race
Time since last natural menstrual period
Vasomotor symptoms (SMART-2)
Vulvar-vaginal atrophy symptoms (SMART-3)

Average participanta

Eligibility criteria
Healthy women postmenopausal women with intact uterus
40 to 65 years
(SMART-1: 40 to 75 years)
34 kg/m2 (32.2 kg/m2 in SMART-1)
All
12 months or 6 months
with appropriate FSH level
7 moderate to severe hot ushes per day or 50 hot
ushes per week
1 moderate to severe vulvar-vaginal symptom (vaginal
dryness, irritation/itching, or pain with intercourse)

Vaginal cytological smear: 5% supercial cells

Vaginal pH: >5
a

53 to 56 years
25 to 26 kg/m2
Caucasian: 76% to 94%
4 to 8 years
10 moderate and severe hot ushes per day
Most bothersome symptom:
Pain with intercourse: 43% to 59%
Vaginal dryness: 30% to 41%
Vaginal itching or irritation: 11% to16%
0.8% to 1.0% supercial cells
Vaginal pH: 6.2

BMI, body mass index; FSH, follicle stimulating hormone; SMART, Selective estrogens, Menopause, And Response to Therapy Trial.
Based on mean baseline characteristic across groups.

(Table 2) [1418]. Efcacy of CE/BZA for VMS has been demonstrated in women experiencing at least 7 moderate to severe hot
ushes per day at baseline [15]. Thus, we recommend CE/BZA for
women with frequent, bothersome hot ushes.
CE/BZA can be considered in women for whom progestins are
inappropriate or for whom the benet-risk prole is assessed as
favorable compared with progestin-containing HT. Recommendations about which to use cannot be made based on efcacy, as
there are few direct comparisons between CE/BZA and EPT. CE/BZA
may be considered for women who have experienced bothersome
vaginal bleeding or breast pain/tenderness, or other intolerable
side effects of progestin-containing therapy (e.g., nausea, hirsutism,
headache, dizziness, weight gain). In addition, exogenous progestins have been associated with cyclical mild depression and
mood symptoms similar to those of premenstrual syndrome or premenstrual dysphoric disorder in postmenopausal women [31,32].
Oral progestin-containing therapy is associated with decreased
glucose tolerance and increased insulin resistance [33,34]. Unlike
ET, EPT has been associated with increased breast density [4,35],
which may impede mammographic detection of breast cancer and
serve as an independent risk factor for breast cancer [36]. Furthermore, given the Womens Health Initiative trial results showing an
increased risk of breast cancer in women taking EPT compared with
ET [3], some women may decline progestin-containing HT based
on concerns about breast cancer risk. Such women may wish to

consider progestin-free treatment with CE/BZA, with the understanding that long-term data on breast cancer risk are not currently
available.
5. Conclusion
CE/BZA is an effective, progestin-free treatment for menopauserelated hot ushes. Unlike EPT, CE/BZA does not increase breast
density. At 10 to 12 months, amenorrhea was reported in about 97%
of the women who received CE/BZA, a rate similar to placebo [12].
Across all the phase 3 studies, VTE was a rare event affecting less
than 1 person per 1000 patients. Thus, CE/BZA lls an important need for a progestin-free alternative to traditional EPT for
nonhysterectomized postmenopausal women who cannot tolerate progestin-containing therapy or who wish to avoid potential
safety concerns associated with progestins. However, when comparing the safety proles of progestin-containing therapy versus
CE/BZA, it should be kept in mind that long-term safety data for
CE/BZA are not yet available.
6. Practice points
CE/BZA is a novel, progestin-free treatment option for managing
symptoms of estrogen deciency in nonhysterectomized postmenopausal women.

Please cite this article in press as: Palacios S, et al. Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deciency
symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003

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CE/BZA should not be used in women with undiagnosed abnormal bleeding, known or suspected breast cancer, or spontaneous
venous or arterial thromboembolism.
Unlike EPT, CE/BZA does not increase breast density.
CE/BZA can be considered in women for whom progestins are
inappropriate or for whom the benet-risk prole is assessed as
favorable compared with progestin-containing HT (e.g., women
with depression, insulin resistance, those who experienced bothersome side effects on progestin-containing therapy).

[2]

[3]

[4]

[5]

7. Research agenda
Menopausal symptoms are chronic and often treated for 5 years.
Data on breast cancer risk and other safety outcomes of CE/BZA
use beyond 2 years are needed.
Further study on VTE risk is needed to conrm the low incidence
seen in the SMART studies.
Further comparative randomized controlled trials of CE/BZA vs
EPT are needed to inform treatment selection.

Disclosures
S Palacios has been a symposium speaker or advisory board
member for Servier, Pzer, GSK, Abbott, Ferrer, Bioiberica, Shionogi
and Amgen and has received research grants and/or consulting
fees from Pzer, Servier, Amgen, MSD, Preglem, Leon Farma, and
Gynea. H Currie has received educational grants and speaker fees,
and has been an advisory board member for several pharmaceutical
and nonpharmaceutical companies. T Mikkola has been a speaker
and/or received consulting fees from AMS, Astellas Pharma, Bayer,
Boston Scientic, Novo Nordisk, and Pzer. E Dragon is an employee
of Pzer Inc.

[6]
[7]
[8]

[9]

[10]

[11]

[12]
[13]
[14]

[15]

Contributors
Santiago Palacios, Heather Currie, Tomi S. Mikkola, and Erika
Dragon contributed equally to the conception of this paper, critically revised it for important intellectual content, and approved the
nal version submitted.
Competing interest
S Palacios has been a symposium speaker or advisory board
member for Servier, Pzer, GSK, Abbott, Ferrer, Bioiberica, Shionogi
and Amgen and has received research grants and/or consulting
fees from Pzer, Servier, Amgen, MSD, Preglem, Leon Farma, and
Gynea. H Currie has received educational grants and speaker fees,
and has been an advisory board member for several pharmaceutical
and nonpharmaceutical companies. T Mikkola has been a speaker
and/or received consulting fees from AMS, Astellas Pharma, Bayer,
Boston Scientic, Novo Nordisk, and Pzer. E Dragon is an employee
of Pzer Inc.
Provenance and peer review

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

Provenance and peer review: Commissioned and externally peer

reviewed. This is a mini review.

[24]

Acknowledgments

[25]

Medical writing assistance was provided by Lela Creutz, PhD and

Lauren Cerruto, of Peloton Advantage, LLC (supported by Pzer).

[26]

References
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[27]

in postmenopausal women; 2006 [cited 2014 May 19]. Available from:

http://www.ema.europa.eu/docs/en GB/document library/Scientic
URL:
guideline/2009/09/WC500003348.pdf
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symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003

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Please cite this article in press as: Palacios S, et al. Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deciency
symptoms of menopause: A practical guide. Maturitas (2015), http://dx.doi.org/10.1016/j.maturitas.2015.01.003