What are the risks of hormone replacement therapy?

Hormone replacement therapy also entails certain risks. Estrogen-based treatment in tablet form carries an increased risk of venous thromboembolism, i.e. the formation of blood clots. Likewise, a high body mass index and other medical history may militate against HRT.

In contrast, studies show that the risk of venous thromboembolism is not increased by transdermal use.1 Transdermal absorption of active substances is generally better tolerated, and this also applies to the use of bio-identical hormones.

For all these reasons, it is important for the patient to have a preliminary discussion with his/her gynaecologist. The aim is to determine exactly what the pros and cons of HRT are, based on the patient's personal situation and individual physical conditions. This risk/benefit profile must be established.

In the case of local disorders exclusively or mainly in the genital area, local treatment is also recommended, e.g. with estrogen-containing vaginal creams or suppositories. Here too, only a small proportion of the active ingredient passes through the skin into the bloodstream, which means that transdermal application is associated with far fewer side effects than tablets.

The WHI Study - Where do we go from here?

The Women's Health Initiative (WHI), published in the USA in 2002, was a large-scale study designed to assess the effects of hormone replacement therapy (HRT) on the health of post-menopausal women. 2 Although the study provided important information, it was also surrounded by controversies and limitations that sparked significant debate in the medical community and beyond.

Indeed, numerous limitations of the WHI study have since been highlighted, such as the age of the population treated (66 to 67 years), the high cardiovascular risk of the participants, the treatment generally started at a distance from the onset of menopause, and the type of treatment (Premarin®, an estrogen-based drug extracted from the urine of pregnant mares).

A number of studies have contradicted the WHI's findings in terms of both vascular and cancer-related effects. For example, the E3N epidemiological study of women in France's Education Nationale confirmed the absence of any increased risk of breast cancer (RR = 1.0) with HRT combining estrogen and micronized natural progesterone, even in the case of long-term treatment (6 years or more) 3 .

How long can hormone replacement therapy be used?

If, with hormone replacement therapy, menopausal symptoms have improved over time, the question arises as to how long the treatment can be continued.

It is now medically proven that HRT should be started as early as possible, ideally as soon as the first symptoms of discomfort appear, but if possible before the age of 60, in order to have a neutral or even protective effect on the risk of cardiovascular disease. 4 The duration of HRT itself is not generally limited. It is important, however, that HRT status is checked at least once a year by the gynaecologist. 5 This makes it possible to assess whether the need for treatment persists, and whether HRT should be adapted by temporarily interrupting it or increasing or reducing doses. 6

What you need to know about hormone replacement therapy (HRT)

  • Before any hormone replacement therapy (HRT), the gynecologist performs a careful analysis of the benefits and risks. 7
  • If you have a history of illness or disease, your gynecologist will probably not prescribe HRT, or will adapt it accordingly.
  • The lowest possible dosage is always defined, which minimizes the risk of side effects.
  • HRT offers additional benefits, as it can have a preventive effect on certain diseases or conditions.

References

    1. Canonico, M et al. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ 2008;336:1227-1231

    2. Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA (2002) 288 (3):321-333

    3. Fournier A. et al. Estrogen-progestagen menopausal hormone therapy and breast cancer: does delay from menopause onset to treatment initiation influence risks? J Clin Oncol 2009;27(31):5138-5143.

    4. Khadilkar SS. Post-reproductive Health: Window of Opportunity for Preventing Comorbidities. J Obstet Gynaecol India. 2019;69(1):1-5

    5. Mueck AO. Anwendungsempfehlungen zur Hormonsubstitution im Klimakterium und Postmenopause. Frauenarzt 2015;56:657-9

    6. Birkhäuser MH. Aktuelle Empfehlungen zur Hormonersatztherapie in der Peri- und Postmenopause Journal für Gynäkologische Endokrinologie 2009;3 (1)

    7. Guideline S3 Peri- and postmenopause - Diagnosis and interventions. Registration number 015 - 062, Updated: January 2020, Version 1.1. https://www.awmf.org/leitlinien/detail/ll/015-062.html