Coronary heart disease
Depending on the age and the duration of menopause, hormone replacement treatment raises the risk of coronary heart disease.
HRT appears to have a diverging effect in menopause, with a decreased risk of heart disease when begun within five years but no effect after ten. If HRT is administered twenty years after menopause, there may be an increase in heart disease. Because of this diversity, some studies have concluded that there is no substantial influence on morbidity. Importantly, regardless of age, there is no variation in long-term morbidity from HRT.
According to a Randomized controlled trial analysis, women who started HRT fewer than 10 years after menopause had lower mortality and coronary heart disease, but no significant effect on stroke or pulmonary embolism risk. Those who commenced medication more than 10 years after menopause did not affect mortality or coronary heart disease, but may have a higher risk of stroke. Both treatments were linked to venous thrombosis and pulmonary embolism.
HRT containing oestrogen and progesterone lowers cholesterol levels as well. HDL levels drop after menopause, while LDL, triglycerides, and lipoprotein levels rise, a pattern that reverses with oestrogen. HRT also reduces platelet aggregation and plaque formation while improving cardiac contraction, coronary blood flow, and sugar metabolism. Through the stimulation of cholesterol ABC transporters, HRT may increase reverse cholesterol transport.
HRT also causes a significant decrease in pro-thrombotic lipoprotein a. Some research on testosterone therapy and cardiovascular disease have found no effect or a modest detrimental effect, while others have seen an improvement in surrogate markers like cholesterol, triglycerides, and weight. Women with reduced testosterone may be at higher risk for heart disease, according to observational research. Testosterone has a favourable influence on vascular endothelial function and tone.
Clotting in the greater saphenous vein; oral oestrogen is linked to an increased risk of venous blood clots in the liver due to increased vitamin K-dependent clotting factor production.
Different oestrogen and progestogen medications, as well as varying doses and ways of usage, may have different effects on venous blood clot formation and the risk of pulmonary embolism. When estrogens are applied to the skin or vaginally, the risk of blood clots is lower, however when they are taken orally, the risk of blood clots and pulmonary embolism is significantly high. Because skin and vaginal hormone therapy do not undergo first-pass metabolism, they lack the anabolic effects that oral hormone therapy has on the liver’s production of vitamin K-dependent clotting components, which could explain why oral hormone therapy may promote blood clot formation.
While a 2018 review found that taking progesterone and oestrogen together can lower this risk, other studies found an increased risk of blood clots and pulmonary embolism when oestrogen and progestogen were combined, especially when treatment began 10 years or more after menopause and the women were over 60.
Bioidentical preparations may lessen the incidence of venous thromboembolism, though studies on this are yet preliminary.
Multiple studies demonstrate that the risk of HRT-related stroke is eliminated if treatment begins within five years of menopause, and that the risk is reduced or even eliminated when HRT is administered by non-oral means. In the WHI, the risk of ischemic stroke was raised throughout the intervention period, but there was no significant effect after the therapy was stopped, and there was no difference in death at long-term follow-up.
Cohort studies in Swedish women have revealed a link with hemorrhagic and ischemic stroke when oral synthetic oestrogen or combination estrogen-progestogen treatment is delayed until 5 years after menopause. Another large cohort of Danish women found that while oral oestrogen raised the risk of stroke, absorption through the skin had no effect, and vaginal oestrogen reduced the risk.
HRT has been linked to endometrial cancer, especially in women who do not use a progestogen.
A continuous combination of oestrogen plus progestin reduces the risk of endometrial cancer in postmenopausal women. To avoid endometrial illness, progestogen therapy should last at least 14 days per cycle.
In the context of hormone replacement, endometrial cancer has been divided into two types. Type 1 is the most prevalent, and it’s usually low-grade. It’s linked to oestrogen therapy. Type 2 cancer is unrelated to oestrogen stimulation, and it has a worse grade and a worse prognosis. Endometrial hyperplasia, which leads to endometrial cancer when oestrogen therapy is used, can be avoided by taking a progestogen at the same time. In the 1970s, there was a dramatic increase in the prevalence of type 1 endometrial cancer due to the widespread use of high-dose estrogens for birth control.
Progestogens, ironically, encourage the growth of uterine fibroids, thus a pelvic ultrasound can be done before starting HRT to ensure that no underlying uterine or endometrial abnormalities are present.
Androgens do not enhance endometrial growth in postmenopausal women and appear to partially block estrogen-induced proliferation.
There isn’t enough high-quality evidence to guide women seeking hormone replacement therapy following endometrial cancer treatment.