Long-term hormonal therapy for menopause (both perimenopause and menopause) can increase the risk of cardiovascular disease, venous thromboembolism, stroke, breast cancer, and bladder disease.

Risks of Long-Term Hormone Therapy for Menopause
Illustration of a woman in the menopause phase
image source: https://www.mazewomenshealth.com

Menopause and Perimenopause 

Menopause is a condition of physiological changes in the female reproductive organs, namely the ovaries' reduced function and the cessation of the ovaries releasing ova. 

Before the menopause phase, there is a phase which is called a perimenopause phase. Perimenopause is a transition phase to menopause. It is characterized by various vasomotor symptoms, menstrual cycle irregularities, mood changes, and sexual function. The hormone estrogen is considered effective in overcoming vasomotor symptoms in perimenopausal and menopausal women. However, long-term administration needs to be monitored because it can cause various side effects, especially on the heart and blood vessels.

A hot flash is when the skin will feel hot suddenly and last for 30 seconds to 5 minutes. In this situation, the skin on the face and neck can become red, the heart rate increases, and there will be a lot of sweat (night sweats).

The existence of changes in reproductive hormones plays an important role in these hot flashes. Decreased estrogen levels can cause thermoregulatory control dysfunction. This dysfunction leads to excessive body heat release and disturbed circulatory rhythm.



Hormonal Therapy in Perimenopausal and Menopausal Phases

Vasomotor symptoms (hot flashes) are the most frequent indication of hormone replacement therapy in perimenopausal patients. And this therapy is approved by the FDA. Transdermal estrogen is considered safer to use than oral estrogens because they can avoid first-pass effects in the liver, thereby reducing the risk of venous thromboembolism.

The hormone estrogen is usually given at the lowest effective dose and is gradually increased after eight weeks of starting therapy. Giving the hormone estrogen can also be combined with the hormone progesterone to reduce endometrial hyperplasia and uterine cancer risk.



Risks and Side Effects of Long-term Hormonal Therapy

The results of a study conducted by Marjoribank et al. stated that the use of hormone therapy could increase the risk of coronary syndrome, venous thromboembolism, stroke, breast cancer, and bladder disorders.

Estrogen hormone therapy can increase the risk of venous thromboembolism 4.28-fold and coronary disease (myocardial infarction or cardiovascular death) 1.89-fold compared with placebo after 1–2 years of therapy. The risk of stroke increased by 1.46-fold after three years of use. Meanwhile, breast cancer and bladder disease risk will increase the risk after 5–6 years of use. However, there was no increased mortality on the use of estrogen hormone therapy or the combination of estrogen-progesterone hormones during the 13-year follow-up of use.

Marjoribank et al. stated that healthy women aged 50-59 years have a low absolute risk of experiencing side effects from low-dose hormone therapy. However, it is necessary to ensure that the patient has no contraindications. In women who do not have a uterus, estrogen hormone therapy for 5-6 years is relatively safe.

The use of estrogen-progesterone hormone therapy has the potential to increase breast cancer risk. Therefore, doctors usually advise patients to stop therapy after three to five years of use. The use of hormone therapy is not recommended in women at risk of cardiovascular disease and breast cancer. Women who are overweight, obese, and have a history of venous thrombosis are contraindicated to oral estrogen hormone therapy, but patients can use transdermal estrogens.


How to deal with the risks or side effects of hormone therapy?

Healthy women who do not have risk factors for heart and blood vessel disease can use low-dose hormone therapy because side effects are quite low. Give estrogen hormone therapy alone for 5-6 years to patients who no longer have a uterus, 

Women who have a history of cardiovascular disease, breast cancer, thromboembolic disease, or obesity should not take the hormone estrogen orally. As an alternative, your doctor may recommend using the transdermal hormone estrogen.



Non-hormonal Alternative Therapy

Several studies suggest that soy products rich in phytoestrogens (isoflavones) can be exogenous estrogen sources and can reduce vasomotor complaints. Unfortunately, a Cochrane meta-analysis stated no conclusive evidence of a benefit of phytoestrogen supplementation for menopause.

There are also non-hormonal alternative therapies to reduce complaints, such as:
  • relaxation therapy, 
  • clonidine, 
  • serotonergic agents, 
  • and gabapentin. 
However, the effectiveness of each of these therapies is controversial or requires further research.


Summary
Perimenopause is a transitional phase characterized by menstrual cycle irregularities, mood changes, and vasomotor symptoms (such as hot flashes and night sweats). A hot flash is the most common hormone therapy indication in women in the perimenopause and postmenopause phases. The hormone estrogen can help regulate the body's temperature and regulate the circadian rhythm to reduce vasomotor symptoms.

Long-term use of the hormone estrogen can cause several effects, such as cardiovascular events, stroke, venous thromboembolism, breast cancer, and bladder disorders. Therefore, it is necessary to check before and during hormone therapy to prevent unwanted side effects.


References
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4. Hill A, Crider M. Hormone therapy, and other treatments for symptoms of menopause. Am Fam Physician. 2016;94(11):884-889.
5. Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database of Systematic Reviews. 2013, issue 12, art. No.: CD001395. Available from: https://doi.org/10.1002/14651858.CD001395.pub4
6. Majoribanks J, Farquhar CM, Roberts H, Lethaby A. Cochrane corner: long-term hormone therapy for perimenopausal and postmenopausal women. Heart. 2018;104(2): 93-96.
7. Santoro N. Perimenopause: from research to practice. J Women's Health. 2016;25(4):332-339.
8. Thurston RC, Joffe H. vasomotor symptoms and menopause: findings from the Study of Women’s Health Across the Nation. Obstet Gynecol Clin North Am. 2011;38(3):489-501.
9. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women’s lives. The American Journal of Medicine. 2005;117(128):145-245.