17 November 2017

TSECs may signal new era for menopause treatment


It’s been 15 years since the US based Women’s Health Initiative (WHI) study scared away a generation of middle-aged women and their clinicians from hormone therapy options for menopause.

The findings of that initial study were found not to be applicable to the younger woman having menopausal symptoms. But the fear created by consumer media around the therapy stuck. Around 60% of women [1],[2] on menopausal hormone therapy (MHT) stopped using it, and a following generation of women were not prepared to go back.

Analysing the totality of available data, including the long-term follow up of the WHI study, all the major medical bodies and colleges have arrived at a global consensus that MHT is the most-effective treatment for moderate-to-severe menopausal symptoms and is most beneficial before the age of 60 years, or, within 10 years of the onset of menopause.3

MHT market use data however, suggests the therapy category still has a brand issue associated with the WHI scare. Two thirds of post-menopausal women will experience vasomotor symptoms (VMS)4 for an average of 7.4 years, with most women rating them as moderate to severe.5a,5b More than 45% will experience moderate-to-severe genitourinary symptoms of menopause (GSM).6 And currently it is thought 66% of post-menopausal women with severe VMS are not treated.6

This appears to be contributed by a combination of the initial WHI study reverberating through generations of women, a reluctance of GPs to engage with patients who have a belief that MHT is dangerous, and some ongoing data around MHT and breast and ovarian cancer which continues to be misunderstood by consumer media.

Last month the Guardian published an article on the latest WHI study publication which confirms that MHT had no effect on all-cause mortality, but they subsequently, and incorrectly, reintroduced the spectre of breast cancer and MHT.7

The advent of a new generation of MHT drugs which provide an alternative to the use of progesterones in preventing endometrial hyperplasia, tissue selective estrogen complexes (TSECs), provides a reason for both patients and clinicians to revisit the menopause conversation — and an opportunity to finally break the hoodoo created by the 2002 WHI study.

TSECs provide relief from VMS, while protecting the uterine tissues from hyperplasia associated with estrogen alone, so there is no need for progestin. Progestin, while protecting against endometrial hyperplasia in women with an intact uterus, can lead to lower glucose tolerance and attenuate the beneficial effects of estrogen. It can also increase mammographic density and is still associated with some increased risk of breast cancer when combined with estrogen.8

The first TSEC available for the management of menopausal symptoms is Duavive. It is a combination of conjugated estrogens and the selective estrogen receptor modulator (SERM), bazedoxifene (BZA). There is now trial data on Duavive which provides the basis to believe that this therapy seems to create the positive effects for VMS while reducing the unwanted estrogenic effects on the uterus, such as endometrial hyperplasia and breakthrough bleeding; and the breast, such as increased density, tenderness and pain.

Duavive is indicated for the treatment of moderate to severe VMS that are associated with menopause in women who still have a uterus. It should be used for the shortest time possible, consistent with treatment goals and risks for the individual woman. There is limited experience with the use of Duavive in women aged over 65 years.

It’s important to note that Duavive should not be used in women who are hypersensitive to conjugated estrogens, bazedoxifene or any of the medicine’s excipients. It should not be used in women who have a known or suspected history of breast cancer, estrogen-dependent malignant tumours, undiagnosed genital bleeding, or untreated endometrial hyperplasia. The treatment should not be used in women who have active venous thromboembolism (VTE) or a history of VTE, arterial thromboembolic disease, or thrombophilic disorder. You also need to avoid use in women who have acute or a history of liver disease, impaired liver function, or porphyria. DUAVIVE should not be used in pregnant women, women who may become pregnant, or breastfeeding women.

Dr Rod Baber, Professor of Obstetrics and Gynaecology at Sydney University, says estrogen deficiency in menopausal women requires a balance of effects in a tissue-dependent manner.

“Duavive’s mode of action provides the benefit of tissue selective agonist and antagonist effects which improves certain menopausal symptoms and quality of life for menopausal women with a uterus, importantly without the need of a progestin. It offers significant and sustained reduction in the frequency and severity of VMS within four weeks of initiating therapy. And it offers a frequency of breast pain tenderness and density, rates of endometrial hyperplasia, and incidents of breakthrough bleeding and spotting, all similar to placebo groups,” Dr Baber said.

For a detailed assessment of this new class of menopause drug, and its implications for a potential step-change to how patients view this therapy class, including a rundown of all the major trial data, watch the video below featuring  Baber.

Click here to watch the webinar: https://www.youtube.com/embed/_bAF0Lt3_f0

Before Prescribing Duavive, please review the full Product Information at https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-02879-1#dec


  1. HRT Benefits and Risks: What you should know, Women’s Health Concern Fact Sheet, British Menopause Society, December 2015
  2. Beverley Lawton, et al, Changes in use of hormone replacement therapy after the report from the Women’s Health Initiative: cross sectional survey of users, BMJ 2003;327:845–6
  3. JAV et al. The 2017 hormone therapy position statement of The North American Menopause Society Menopause. The Journal of The North American Menopause Society217; 24 (7):  728-753.
  4. Williams RE et al, Climacteric. 2008 Feb;11(1):32-43.
  5. Aves et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Internal Medicine, 2015; 175(4), p.531.
  6. Palacios S et al, Climacteric, 2015, 18 Supp 1
  7. Sarah Bosely, HRT won’t kill you but menopausal women still face a difficult decision, The Guardian, Sept 2017
  8. Prof Rod Baber, Webinar, TSEC – the next generation of MHT, 2017, www.herhealth.com.au

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Pfizer Australia Pty Ltd. 38-42 Wharf Road, West Ryde, NSW 2114. Medical Information: 1800 675 229. Date of Preparation October 2017. PP-DUA-AUS-0223.