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Breaking Down the Latest Study on Women Over Age 65 and Hormone Therapy Use

Breaking Down the Latest Study on Women Over Age 65 and Hormone Therapy Use

By: Holly L. Thacker, MD • Posted on October 08, 2024

After the 2002 Women’s Health Initiative, the number of American women aged 65 and older who used Hormone Therapy (HT) significantly decreased, which is very unfortunate as estrogen deficiency does NOT disappear with age. This is also concerning because overall health outcomes are better in women who take HT. 

Risks for mortality, certain cancers and cardiovascular outcomes do vary by hormone therapy type. This is why this latest study on hormone therapy is so important.

Just because a woman is several years since the Last Menstrual Period (LMP) does not mean that vasomotor symptoms like hot flashes and hot flushes go away. For some women, vasomotor symptoms can last decades. In addition, women who are postmenopausal are at an increased risk for osteoporosis, bone loss and the majority of women will experience various degrees of Genitourinary Syndrome (GSM).

The authors of this latest study looked at prescription drug and medical records in over 10.9 million from the Centers of Medicare Services (CMS) and the possible health outcomes based on the types of estrogen, progestins, as well as routes of administration (oral, transdermal, and vaginal) and strengths. The study evaluated these prescriptions on the following: 

  • all-cause mortality
  • cancers such as breast, ovarian, endometrial, lung and colorectal cancer
  • heart disease
  • congestive heart failure (CHF)
  • deep vein thrombosis (DVT)
  • atrial fibrillation
  • myocardial infarction (heart attack)
  • dreaded dementia

Only 14 percent of these women over age 65 used any type of HT during this 13 year time frame. Furthermore, the percent of women aged 65 and older using ANY HT declined from 11.4% at the beginning of the study to only 5.5% in 2020 at the end of the study.

By the early part of this study, we knew from the WHI that women on HT had decreased death rates so it is concerning that use continues to plummet. Death incidence was much lower among HT users than non HT users (6.3 vs 12.6 per 1,000 person years). Socioeconomic, health status was not randomized, but such a large observation study - that it is very important and Medicaid eligibility from special supplement - were a proxy for income level. 

Vaginal, transdermal and oral HT were associated with a 30%, 20% and 11% reduction in mortality risk. Looking at women who had used estrogen alone compared to those that had never used estrogen or who had stopped it had reductions in death rate, several cancers and heart problems! 

Lower doses along with transdermal preparations and vaginal estrogen had better risk reduction profiles:

  • 19% for mortality (adjusted Hazard Rate (HR) = 0.81; 95% CI, 0.79-0.82)
  • 16% for breast cancer (adjusted HR = 0.84; 95% CI, 0.83-0.86)
  • 13% for lung cancer (adjusted HR = 0.87; 95% CI, 0.84-0.9)
  • 12% for colorectal cancer (adjusted HR = 0.88; 95% CI, 0.84-0.91)
  • 5% for congestive heart failure (adjusted HR = 0.95; 95% CI, 0.94-0.96)
  • 3% for venous thromboembolism (adjusted HR = 0.97; 95% CI, 0.96-0.98)
  • 4% for atrial fibrillation (adjusted HR = 0.96; 95% CI, 0.95-0.98)
  • 11% for acute myocardial infarction (adjusted HR = 0.89; 95% CI, 0.87-0.92)
  • 2% for dementia (adjusted HR = 0.98; 95% CI, 0.97-1)

Those who took Conjugated Equine Estrogen (Premarin®) saw a 23% reduced risk of breast cancer while “bioidentical” estradiol showed a 12% risk of breast cancer. Injectable estrogens were associated with an increased risk of heart disease and high dose oral estrogen was associated with an increased risk of stroke by 8% and dementia by 3%.

Overall the use of HT alone is 10 times greater than Estrogen-Progestogen Therapy (EPT) or progesterone alone and TWICE as many women were on vaginal estrogen. Half of the women with a hysterectomy have had their ovaries/tubes removed and that can affect the reduction in breast cancer and ovarian cancer.

Conjugated Equine Estrogen (CEE) in WHI was associated with a 6% mortality reduction in the 18 year follow up and gives plausibility to the 9% mortality reduction this study observed with use of medium dose oral CEE. In addition, the 19% mortality reduction with Estrogen Therapy (ET) is consistent with 31 observation studies and Randomized clinical trial (RCT) that have reported reduced death rates in HT users. Use of estrogen plus progestin combination therapy were associated with significant risk reductions of:

  • 45% for endometrial cancer (aHR = 0.55; 95% CI, 0.5-0.6)
  • 21% for ovarian cancer (aHR = 0.79; 95% CI, 0.71-0.89)
  • 5% for ischemic heart disease (aHR = 0.95; 95% CI, 0.93-0.97)
  • 5% for congestive heart failure (aHR = 0.95; 95% CI, 0.91-0.98
  • 5% for venous thromboembolism (aHR = 0.95; 95% CI, 0.91-0.99)
  • Conversely, estrogen plus natural progesterone was associated with a risk reduction of 4% for congestive heart failure (aHR = 0.96; 95% CI, 0.92-1)

Estrogen plus progestogen therapy, regardless of progestogen type, had no significant association with mortality. Both estrogen plus progestin and estrogen plus progesterone combination therapies were associated with a 10% to 19% increased risk of diagnosis for breast cancer. However, risk was mitigated when using low-dose vaginal and transdermal estradiol plus progestin combination therapy.

Interestingly, progesterone monotherapy was associated with a 22% reduced risk for mortality, a 10% reduced risk for breast cancer and a 19% reduced risk for lung cancer. Progestin monotherapy was associated with an 11% increased risk for mortality, a 21% increased risk for breast cancer diagnosis and a 14% increased risk for lung cancer diagnosis.

This study is a major contribution and should be reassuring. Denying HT, especially local vaginal estrogen, but any HT is ageist and sexist!

Be Strong, Be Healthy, Be in Charge!

-Holly L. Thacker MD

About Holly L. Thacker, MD, FACP

Holly L. Thacker, MD, FACP is nationally known for her leadership in women’s health. She is the founder of the Cleveland Clinic Specialized Women’s Health Fellowship and is currently the Professor and Director of the Center for Specialized Women’s Health at Cleveland Clinic and Lerner College of Medicine at Case Western Reserve University. Her special interests are menopause and related medical problems including osteoporosis, hormone therapy, breast cancer risk assessment, menstrual disorders, female sexual dysfunction and interdisciplinary women’s health. Dr. Thacker is the Executive Director of Speaking of Women’s Health and the author of The Cleveland Clinic Guide to Menopause.

women's health, hormone therapy, ht, hormone replacement therapy, estrogen, estrogen therapy, menopause, postmenopause, hrt, dr. holly thacker

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