canadian menopause society société canadienne de la … · professor of obstetrics and gynecology...

SIGMA Canadian Menopause Society is proud to present the

2017 SIGMA Distinguished Lecture Series

Date: Friday September 22, 2017Time: 6:00 to 9 PMSpeaker: Dr. JoAnn PinkertonModerator: Dr.Chui Kin YuenTopic: Clinical Utilities of TSEC, a Novel Hormonal Therapy for Menopausal Women

AGENDA:18:00 - 18:30 Reception18:30 - 20:00 Dinner & Lecture20:00 - 20:20 Q and A

RSVP: by September 15, 2017 either Phone 604-736-7267 or Fax 604-736-7268 or email: [email protected]

CANADIAN MENOPAUSE SOCIETY

Société canadienne de la ménopause



Venue: Glowbal, 590 W Georgia St., Vancouver Phone: 604-602-0835

OBJECTIVES

Novel Hormone Therapy- Conjugated Estrogens/Bazedoxefine(CE/BZA): Whom to Consider Therapy and Why

(1) Understand new options compared to traditional HT

(2) Describe the concept of Tissue Selective Estrogen Compound (TSEC) (3) Results from SMART 5 trials on CEE/BZA

VMS and Sleep Bone Vagina Safety- endometrium, breast and heart Adverse events- VTE risk

(3) Differentiate on basis of bleeding and breast tenderness between CE/BZA (TSEC) and CE/MPA (EPT)

Dr. JoAnn Pinkerton is a Professor of Obstetrics and Gynecology and Division Director of Midlife Health Center at the University of Virginia Health System in Charlottesville, Virginia, Executive Director of North American Menopause Society (NAMS) since October 2015 and became President of South Atlantic Association of Obstetrics and Gynecology SAAOG in 2016. She is a certified Menopause Specialist, a longtime fellow of ACOG , 2008-09 President of NAMS and as served on many national and international committees and local University of Virginia Committees. Awards include the 2013 UVA Sharon Hostler Women in Leadership award, BEST DOCTORs and TOP DOCTORS in America since 2010. She won an American Library Association Award for her book, Understanding Midlife Health. She is the Associate Editor for the Journal Menopause and the section director for menopause for the Journal of Women’s Health. She serves on the Editorial Boards for Menopause and Climacteric. She has published more than 100 peer-reviewed publications, 30 invited papers and 11 invited chapters and served as PI for over 30 clinical trials on treatment of hot flashes with hormonal and non-hormonal therapies. She is a strong proponent of education at the national level as well as within the community, holding Midlife Community Educational Symposiums-two per year to allow tailored education appropriate for different backgrounds.

She is married and the mother of three children, Jeremy, (deceased 2010 MVA), Katie, who is married and has a Masters in graphic design, and Liz, who is a second year medical student at Wake forest. She provides medical safety for the Women’s 4 mile Breast Cancer Training Program, runs herself, and plays mandolin.





JoAnn V Pinkerton, MD, FACOG, NCMP





ABstrACtNovel Hormone Therapy – Conjugated Estrogens/Bazedoxefine: Whom to Consider for Therapy, and Why?JoAnn V. Pinkerton, MDExecutive Director, North American Menopause SocietyProfessor of Obstetrics and GynecologyUniversity of Virginia Health System; Charlottesville, Virginia

The 5 Phase 3 clinical trials known as the sMArt trials (Selective estrogens, Menopause, And Response to Therapy) were conducted in postmenopausal women with a uterus. The trials demonstrated the efficacy and safety of conjugated estrogens (CE) combined with the selective estrogen-receptor modulator (SERM)bazedoxifene (BZA), CE/BZA for symptomatic relief, while preventing endometrial hyperplasia without need for a progestogen.

Vasomotor symptoms. In postmenopausal women with moderate-to-severe vasomotor symptoms (SMART-1 subset trial; SMART-2 trial), CE 0.45 mg/BZA 20 mg reduced hot flush frequency and severity at 12 weeks vs placebo (P<.05). Hot flush frequency was reduced by 74% for CE 0.45 mg/BZA 20 mg vs 51% for placebo.

Bone. In SMART-1, CE 0.45 mg/BZA 20 mg prevented loss of bone mass in the lumbar spine and hip in postmenopausal women at risk for osteoporosis (P<.01).3 Lumbar spine BMD increased from baseline by1.05%, whereas a loss of 1.81% with placebo was seen at 12 months; at 24 months, lumbar spine bone mineral density had increased by 1.6%, vs a loss of 1.8% for placebo. Fracture prevention has been reported for the use of BZA alone, but no randomized, controlled trials have been conducted with CE/BZA.

Vulvar-vaginal atrophy. In SMART-1 and -3, 2 doses of CE/BZA—CE 0.45/BZA 20 and CE 0.625/BZA20 mg—were compared with placebo in postmenopausal women with vulvar and vaginal atrophy, CE 0.45/BZA 20 mg increased vaginal superficial and intermediate cells and decreased parabasal cells vs placebo after 12 weeks of treatment. Women receiving active treatment also had a lower incidence of dyspareunia (P<.05 for both doses) at weeks 9 and 12 (P<.05).

Breast pain and tenderness. In SMART-5, the effect of CE 0.45 mg/BZA 20 mg on breast pain and tenderness was similar to that of placebo, showing a decrease of 5% to 8% for both, while in the same study CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg increased it by 20%-24% (P<.001). Similarly, the effect of CE 0.45 mg/BZA 20 mg on breast density was similar to that of placebo at 1 year, whereas CE 0.45 mg/MPA 1.5 mg significantly increased breast density vs placebo (P<.001). Rates of breast cancer for women treated with CE 0.45 mg/BZA 20 mg were similar to placebo for up to 2 years.

Endometrial hyperplasia. No increase in endometrial hyperplasia was observed with CE 0.45 mg/BZA 20 vs placebo (<1%) at 1 and 2 years. Endometrial thickness increased from baseline (<1 mm) after 2 years, comparable to placebo. High rates of amenorrhea were reported; and bleeding and spotting for women treated with CE 0.45 mg/BZA 20 mg were less than with CE 0.45 mg/MPA 1.5 mg.11 In SMART-5, cumulative amenorrhea rates were >87% for CE 0.45/BZA 20 mg, >83% for placebo, and >54% for CE 0.45/MPA 1.5 mg. Rates of endometrial cancer were not increased with CE 0.45 mg/BZA 20 mg for up to 2 years.





Cardiovascular events. In the women aged 40 to 65 years treated with CE 0.45 mg/BZA 20 mg, the rates of cardiovascular and cerebrovascular events, cancers (breast, endometrial, ovarian), and mortality were similar to placebo. With BZA 20 mg used alone, a 2-fold increased risk of venous thromboembolism was seen, but no additive effects with CE/BZA was evident.

rEFErENCEs• Lobo RA, Pinkerton JV, Gass ML, et al. Evaluation of bazedoxifene/

conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril. 2009;92(3):1025-1038.

• Pinkerton JV, Utian WH, Constantine GD, Olivier S, Pickar JH. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial. Menopause. 2009;16(6):1116-1124.

• Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex (TSEC) of bazedoxifene/conjugated estrogens (BZA/CE) for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009;92(3):1045-1052.

• Pinkerton JV, Harvey JA, Lindsay R, Pan K, Chines AA, Mirkin S, et al; SMART-5 Investigators. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. J Clin Endocrinol Metab. 2014;99(2):E189-E198.

• Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause. 2010;17(2):281-289.

• Pinkerton JV, Komm BS, Mirkin S. Tissue selective estrogen complex combinations with bazedoxifene/conjugated estrogens as a model. Climacteric. 2013;16(6):618-628.

• Harvey JA, Pinkerton JV, Baracat EC, Shi H, Chines AA, Mirkin S. Breast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens. Menopause. 2013;20(2):138-145

• 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.

• Pickar JH, Yeh IT, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex (TSEC) containing bazedoxifene/conjugated estrogens as a menopausal therapy. Fertil Steril. 2009;92(3):1018-1024.

• Archer DF, Lewis V, Carr BR, Olivier S, Pickar JH. Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women. Fertil Steril. 2009;92(3):1039-1044.

• Mirkin S, Komm BS, Pan K, Chines AA. Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. Climacteric. 2013;16(3):338-346.

• Mirkin S, Archer DF, Taylor HS, Pickar JH, Komm BS. Differential effects of menopausal therapies on the endometrium. Menopause. 2014;21(8):899-908.

canadian menopause society société canadienne de la … · professor of obstetrics and gynecology...

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