Competent Menopausal Hormone Therapy Is Safe After 65

In 2002, the Women’s Health Initiative investigated how hormone therapy (HT) affects the risk of developing serious illnesses in postmenopausal women. According to their conclusions, menopausal therapy with estrogen and progestogen in women with an average age of 63 increased the incidence of invasive breast cancer, stroke, and ischemic heart disease, although it decreased the number of fractures. As a result, many women discontinued hormone therapy to reduce menopausal symptoms and correct the consequences of estrogen and progesterone deficiency.

Researchers from the National Institutes of Health (NIH) conducted a comprehensive analysis of hormonal therapy use after the age of 65. They examined the health outcomes of HT based on the type, route, and dose of estrogen/progestogen.

Hormone Therapy and Menopausal Symptoms

Until recently, it was often believed that women did not need hormone therapy after menopause, as it was assumed that serious menopausal symptoms did not persist in women aged 65 and older. However, research has shown that vasomotor symptoms of menopause persisted for 7–12 years in many women. Certain symptoms persisted in 42.1% of women aged 60-65.

For healthy women with persistent vasomotor symptoms, continuing hormone therapy after 65 years of age is an effective way to improve life quality. Of course, this requires specialist advice and ongoing assessment of risks and benefits. Such therapy is now recognized as the most effective treatment option for a range of unpleasant symptoms associated with menopause. For information on these symptoms and a detailed overview of menopausal transition, refer to our Menopause Guide.

Additionally, risks can be reduced by choosing low doses, non-oral route, and various types of estrogens and progestogens. However, verified information on the impact of different forms of hormone therapy, dosages, and routes of administration is lacking.

New Study Methods

The study is based on records of over 10 million senior Medicare women from 2007 to 2020. Medicare is a U.S. government health insurance program for individuals aged 65 and older, as well as younger people with disabilities. Researchers limited participation in the study to women who first became eligible for Medicare at approximately 65 years old with available data for at least six months. The authors investigated the impact of different menopausal hormone therapy (MHT) regimens on all-cause mortality, five types of cancer, six cardiovascular diseases, and dementia.

The types of cancer studied included breast, lung, endometrial, ovarian, and colorectal cancers. Cardiovascular diseases included ischemic heart disease (IHD), heart failure (HF), venous thromboembolism, stroke, atrial fibrillation, and acute myocardial infarction.

The study considered various dosages and routes of medications: oral, transdermal, vaginal, and injectable. The authors included three types of estrogen (estradiol, conjugated estrogen, and ethinyl estradiol), two types of progestogen (progesterone [natural] or progestin [synthetic]), and a total of nine different combinations of progestogens and estrogens, as well as the use of only one type of hormone. Ethinyl estradiol was never prescribed alone and was always combined only with progestin.

Results

Hormone therapy was fully justified by the study authors. The results indicated that different dosages, hormones, and routes significantly influence the risks of developing dangerous conditions and mortality.

Hormone Therapy and All-Cause Mortality

All-cause mortality decreased by 19% among women using estrogen therapy (ET) compared to those not taking hormones. This represents 113,226 fewer deaths than could have occurred. Vaginal, transdermal, and oral hormone administration were associated with a 30%, 20%, and 11% reduction in mortality risk, respectively. Mortality risks associated with low and medium doses of ET were significantly lower than with high doses, but did not differ from each other. Combined estrogen-progestogen therapy did not show a significant reduction in mortality. Progesterone monotherapy was associated with a 22% reduction in mortality risk, while progestin monotherapy was associated with an 11% increased risk.

Cancer Risks Associated with HT

ET reduced the risk of breast cancer overall by 16%, but there were differences depending on the hormone route and type. Specifically, the oral route was more effective than vaginal and transdermal. Additionally, conjugated estrogen was associated with a greater (23%) reduction in breast cancer risk than estradiol (12%). Approximately 70% of oral medium doses of estradiol were 0.625 mg, and this dosage was associated with a 26% reduction in breast cancer risk. Estrogen + progestin and estrogen + progesterone, on the other hand, increased the risk of breast cancer by 19% and 10%, respectively. Low doses of vaginal and transdermal progesterone + estradiol did not demonstrate such an increase. Progesterone alone was associated with a 10% reduction in breast cancer risk, while progestin increased the risk by 21%.

ET reduced the risk of lung cancer and colorectal cancer by 13% and 12%, respectively. Both estrogen + progestin and estrogen + progesterone showed no risk for these two types of cancer. Among 24 different combinations of progestogen-estrogen therapy, oral medium doses of progestin + estradiol demonstrated a 16% reduction in lung cancer risk. But the oral low doses of progestin + conjugated estrogen or estradiol showed a 17%-20% reduction in colorectal cancer risk. Progesterone monotherapy was associated with a 19% reduction in lung cancer risk, while progestin increased the risk by 14%.

Progestin + estrogen reduced the risk of endometrial cancer by 45%, while progesterone + estrogen demonstrated a 33% increase in such risk.

Hormone Therapy and Risk of Cardiovascular Diseases and Dementia

ET was predominantly associated with an increased risk of IHD by 3-4%, and with injectable administration, the risk increased by 17%. However, low doses of conjugated estrogen or estradiol orally reduced the risk of this disease by 1-2%. Progestin alone did not affect the risk of ischemic heart disease, while progesterone increased it by 8%. On the other hand, progestin + estrogen reduced the risk of ischemic heart disease and heart failure by 4-5%. High doses of injectable estrogen increased the risk of heart failure by 5-17%. In the same time, in other forms and doses, they reduced the risk of this disorder by 5%.

Transdermal and vaginal application of estrogens showed a decrease in the risk of stroke and dementia by <10%. Conversely, high doses of estrogens increased the risk of both conditions by 8% and 3%, respectively. Low doses of oral progestin + conjugated estrogen or estradiol and progesterone + estradiol reduced the risk of stroke and dementia by 6-10% and 10%, respectively. Low doses of oral progestin + conjugated estrogen reduced the risk of all six cardiovascular diseases by 5-13%.