# Atherosclerosis Intervention with Novel Tissue Selective Estrogen Complex Therapy

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $2,803,461

## Abstract

PROJECT SUMMARY/ABSTRACT
The clinical and public health implications of this proposed trial are far-reaching as the science over the last
decade has confirmed that estrogen provides substantial benefits with low risk to women especially when
initiated in the perimenopausal or early postmenopausal period. However, the majority of women entering
menopause have a uterus requiring co-treatment with progestogen to counter estrogen-induced endometrial
hyperplasia. Co-treatment with progestogen creates a limiting factor for postmenopausal hormone therapy
(HT) since relative to estrogen alone, traditional progestogen-containing HT regimens carry the greatest health
risks for women, including venous thromboembolism (VTE) and breast cancer. However, as a component of
tissue selective estrogen complex (TSEC), a new class of agents, estrogen can now be delivered in a
progestogen-free regimen without risks from progestogen exposure. As a new class of innovative medications,
TSEC therapy provides a novel approach for the treatment of menopausal symptoms by partnering a selective
estrogen receptor modulator (SERM) with estrogen to achieve optimal clinical results based on the blended
tissue-selective activity profile. The effect of combined bazedoxifene (BZA), a third generation SERM with
conjugated estrogens (CE) on breast, endometrium, bone, lipid biosynthesis and venous thrombosis are
unique with optimization of safety and efficacy. A series of phase 3 randomized controlled trials have shown
that BZA/CE (FDA approved) is effective in preventing osteoporosis and providing relief of vasomotor and
vaginal symptoms while ensuring endometrial safety. BZA/CE does not stimulate endometrial tissue and the
rate of cumulative amenorrhea with BZA/CE is comparable with placebo as is the incidence of endometrial
hyperplasia (<1%). In addition, BZA/CE does not stimulate breast tissue and does not increase mammographic
density relative to placebo; the incidences of VTE (deep vein thrombosis and pulmonary embolism) and stroke
are similar to placebo. To date, randomized controlled trials have been conducted with traditional progestogen-
based HT. Deploying the innovative progestogen-free formulation of BZA/CE to protect the uterus in women
without a hysterectomy is the next step beyond traditional HT (progestogen opposed estrogen therapy) in
providing safe and effective therapy for women with the new TSEC class of agents, the effects of which on
atherosclerosis progression are unknown. This proposal seeks to address this major gap in our knowledge and
to cease upon this unique public health opportunity. The specific aim of our proposal is to conduct a
randomized, double-blinded, placebo-controlled trial in 360 healthy postmenopausal women with a uterus
within 6 years of menopause and less than 60 years of age without clinical cardiovascular disease and
diabetes mellitus randomized to BZA 20 mg/CE 0.45 mg or placebo for a treatment period of 2 to 4.5 years to
determine the ef...

## Key facts

- **NIH application ID:** 10694230
- **Project number:** 5R01AG058691-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Howard Neil Hodis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,803,461
- **Award type:** 5
- **Project period:** 2019-03-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694230

## Citation

> US National Institutes of Health, RePORTER application 10694230, Atherosclerosis Intervention with Novel Tissue Selective Estrogen Complex Therapy (5R01AG058691-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10694230. Licensed CC0.

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