Patient considerations in the management of menopausal symptoms: role of conjugated estrogens with bazedoxifene

Figures & data

Figure 1 Changes in estimated proportion of women aged 45–69 years using menopausal hormone therapy in 17 European countries from 2002 to 2010 (A). Changes in estimated proportion of women aged ≥40 years reporting current use of oral postmenopausal hormones from 1999 to 2010 in the USA (B).

Notes: (A) Reprinted from Maturitas, 2014;79(3), Ameye L, Antoine C, Paesmans M, de Azambuja E, Rozenberg S, Menopausal hormone therapy use in 17 European countries during the last decade, Pages 287–291,²⁶ Copyright ©2014, with permission from Elsevier. (B) Data from Sprague et al.²⁷

Figure 2 Incidence of breast pain during treatment with transdermal estradiol/oral micronized progesterone, oral CE/oral micronized progesterone, or placebo in women with and without baseline pain in KEEPS.

Note: P=0.18 for Pearson’s chi-square test of differences among treatment groups versus baseline.
Abbreviations: CE, conjugated estrogens; KEEPS, Kronos Early Estrogen Prevention Study.

Table 1 Effects of CE/BZA on BMD at month 12 in SMART-1,& SMART-4,# and SMART-5$ (data on file)

	BMD, adjusted mean (SE) percentage change from baseline at month 12
	CE 0.45 mg/BZA 20 mg	CE 0.625 mg/BZA 20 mg	CE 0.45 mg/MPA 1.5 mg	Placebo
SMART-1 substudy Ia
Lumbar spine	1.45 (0.25)*	1.59 (0.25)*	–	−1.14 (0.25)
Total hip	1.06 (0.17)*	1.10 (0.17)*	–	−0.44 (0.17)
Femoral neck	0.65 (0.21)*	0.58 (0.21)*	–	−0.67 (0.21)
Femoral trochanter	1.86 (0.28)*	1.72 (0.28)*	–	−0.09 (0.28)
SMART-1 substudy IIa
Lumbar spine	1.08 (0.28)*	1.05 (0.29)*	–	−1.78 (0.29)
Total hip	0.64 (0.20)*	0.26 (0.21)*	–	−0.86 (0.21)
Femoral neck	−0.16 (0.29)**	0.12 (0.30)*	–	−1.27 (0.29)
Femoral trochanter	0.79 (0.27)*	0.85 (0.28)*	–	−1.07 (0.28)
SMART-4
Lumbar spine	0.80 (0.24)*	0.80 (0.24)*	2.22 (0.37)*	−1.56 (0.35)
Total hip	0.62 (0.19)*	0.84 (0.19)*	1.47 (0.29)*	−0.99 (0.27)
Femoral neck	0.53 (0.24)*	0.69 (0.24)*	0.20 (0.36)*	−1.95 (0.34)
Femoral trochanter	1.20 (0.24)*	1.18 (0.24)*	2.29 (0.36)*	−1.05 (0.34)
SMART-5
Lumbar spine	0.24 (0.29)*	0.60 (0.27)*	1.30 (0.39)*	−1.28 (0.28)
Total hip	0.50 (0.20)*	0.89 (0.18)*	0.71 (0.26)*	−0.72 (0.18)
Femoral neck	−0.07 (0.26)**	0.84 (0.24)*	0.52 (0.34)*	−1.00 (0.24)
Femoral trochanter	1.31 (0.31)*	1.57 (0.29)*	1.35 (0.41)*	−0.29 (0.29)

Notes:

a SMART-1 substudy I: women >5 years postmenopausal; SMART-1 substudy II: women 1–5 years postmenopausal. Both substudies enrolled women with lumbar spine or total hip BMD T-scores between −1 and −2.5 (inclusive) and at least one additional osteoporosis risk factor at screening. Risk factors included Caucasian or Asian race, early menopause (≤40 years of age), family history of osteoporosis, current smoking, low-calcium diet, history of excessive alcohol use, inactive lifestyle, and a thin and/or small frame (weight <50 kg and/or BMI <18 kg/m²).

* P<0.001 versus placebo.

** P<0.01 versus placebo.

& Reprinted from Fertil Steril, 2009;92(3), Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G, Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estro gens for osteoporosis prevention in at-risk postmenopausal women, pages 1045–1052,⁸² Copyright ©2009, with permission of Elsevier.

# Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women, Mirkin S, Komm BS, Pan K, Chines AA, Climacteric, 2013;16(3):338–346,⁸³ reprinted by permission of the publisher (Taylor and Francis Ltd, http://www.tandfonline.com).

$ Adapted with permission of Endocrine Society, from Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial, Pinkerton JV, Harvey JA, Lindsay R, et al; SMART-5 Investigators, J Clin Endocrinol Metab, 2014;99(2):E189–E198,⁸⁴ Copyright © 1952; permission conveyed through Copyright Clearance Center, Inc.

Abbreviations: CE, conjugated estrogens; BZA, bazedoxifene; BMD, bone mineral density; SMART, Selective estrogens, Menopause, And Response to Therapy; SE, standard error; MPA, medroxyprogesterone acetate; BMI, body mass index.

Figure 3 Percentage of women reporting ≥1 day of breast tenderness in daily diaries during 4-week intervals through 12 weeks in SMART-5.

Notes: *P<0.001 for CE/MPA versus all other treatment groups. There were no statistically significant differences between either dose of CE/BZA and placebo. Pinkerton JV, Harvey JA, Pan K, et al. Breast effects of bazedoxifene-conjugated estrogens: a randomized controlled trial. Obstet Gynecol. 2013;121(5):959–968.⁹⁴ Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer Health. Please contact [email protected] for further information.
Abbreviations: SMART, Selective estrogens, Menopause, And Response to Therapy; CE, conjugated estrogens; MPA, medroxyprogesterone acetate; BZA, bazedoxifene.

Figure 4 Bleeding/spotting rates over 1 year of treatment with CE/BZA compared to CE/MPA in SMART-5.¹⁰⁴

Note: P<0.001 for all values versus CE/MPA.
Abbreviations: CE, conjugated estrogens; BZA, bazedoxifene; MPA, medroxyprogesterone acetate; SMART, Selective estrogens, Menopause, And Response to Therapy.

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