Impact of menopause on women

The 2022 Menopause Foundation of Canada’s The Silence and the Stigma: Menopause in Canada report, showed >95% of women experience symptoms related to menopause, such as hot flushes, cognitive changes, sexual dysfunction, sleep disturbances and mood swings, which severely impact their QoL.²

About 50% of women reported that they were unprepared for menopause and felt the topic is still taboo. Another 40% said they felt alone, and that knowledge of the symptoms associated with menopause were lacking.²

Furthermore, the report found that while women trust their family physician, when they proactively discuss menopause with them, 75% found their advice unhelpful or only somewhat helpful, and 40% felt their symptoms were undertreated.²

Both the British Menopause Society (BMS) and the North American Menopause Society (NAMS) recommend HT as the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause.^3,4

Timing of initiation

The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) recommend the use of HT should be based on consideration of all risk factors for CV disease, age, and time from menopause.⁶

The BMS and NAMS recommend HT for women <60-years or within 10 years of menopause-onset without contraindications, the benefits outweigh the risks for treating bothersome symptoms and preventing bone loss.^3,4

According to NAMS, for women >60-years or starting HT more than 10 years after menopause onset, the benefit-risk ratio may be less favourable due to increased risks of certain conditions. In such cases, alternative therapies should be considered, like low-dose vaginal oestrogen therapy or other options.³

The decision whether to take HRT, the dose, and its the duration should be made on an individualised basis after discussing the benefits and risks with each patient.^3,4

According to the BMS recommendations the decision should be based on the overall benefits obtained from using HT including symptom control and improving QoL, as well as considering the associated bone and CV benefits. The society also states that arbitrary limits should not be placed on the duration of usage of HT if symptoms persist. The advantages and disadvantages should be evaluated annually.⁴

What about type and route of administration?

Various formulations (oestrogens and progestogens) and routes are available to allow for an individualised approach to menopause care. Oestrogen therapy alone is used for post-menopausal women who have undergone a hysterectomy.⁸

Oestrogen formulations include human estrogen -17ß-estradiol (E2, which is the primary oestrogen produced by the ovaries and most biologically active), animal-derived oestrogens (CEE), and synthetic oestrogens (ethinyl oestradiol (EE). CEE is comprised of a mixture of estrogens derived from the urine of pregnant mares.⁸

Progestogen therapy is used to avoid the increased risk of endometrial cancer for a woman with an intact uterus on systemic oestrogen, as unopposed oestrogen thickens the uterine lining. Progestogen options include micronised progesterone (body-identical) and synthetic progestins.⁸

The BMS recommends using progestogens in a sequential or continuous combined regimen to minimise the risk of endometrial hyperplasia and cancer.^3,4

Oestrogens are absorbed well through the gastrointestinal (GI) tract, skin, and mucus membranes. Formulations are available as oral preparations, transdermal patches and gel, vaginal preparations, and in combination with progestogen.⁸

Risks of oral oestrogens largely stem from first pass metabolism through the liver and include increased production of coagulation factors and various inflammatory markers, hypertriglyceridemia, and elevated risk of venous thromboembolism (VTE), and gallstones.⁸

Because of the avoidance of the first pass metabolism, the transdermal preparations have less impact on triglycerides, coagulation factors and gallbladder disease.⁸

The BMS recommendations, based on a comprehensive overview of potential risks associated with the use of HT, recommends transdermal administration of oestradiol as the first-choice route due to its lower risk of venous thrombosis and stroke compared to oral administration.⁴

The AACE/ACE also recommend the use of transdermal as compared with oral oestrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease.⁶

The appropriate, often lowest, effective dose of systemic oestrogen that provides benefits and minimises risks for the individual woman should be the therapeutic goal.³

Micronised progesterone and dydrogesterone are suggested as alternatives to oral progestogens, as they are less likely to increase the risk of venous thrombosis and breast cancer (BCa). A history of BCa is considered a contraindication to systemic HT. The AACE/ACE also recommends the use of micronised progesterone because it is considered the safer alternative.^4,6

In South Africa, transdermal HT is available as patches (oestrogen-only and combined estrogen/progestin) and gel. For non-hysterectomised patients using transdermal gel, progestogen must be supplied separately .⁷

Conclusion

Overall, recommendations by menopause societies emphasise the benefits of HT. They recommend individualised treatment choices based on the best available evidence to maximise benefits and minimise risks for women undergoing HT.

References

1. Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas), 2019.
2. Menopause Foundation of Canada. The Silence and the Stigma: Menopause in Canada. 2022. [Internet]. Available at: https://menopausefoundationcanada.ca/
3. The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause, 2022.
4. Hamoda H, Panay N, Pedder H, et al. The British Menopause Society &Women’s Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reproductive Health, 2020.
5. Genazzani AR, Monteleone P, Giannini AG, and Simoncini T. Hormone therapy in the postmenopausal years: Considering benefits and risks in clinical practice. Human Reproduction Update, 2021.
6. Cobin RH, Goodman NF on behalf of the AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on Menopause–2017 Update. Endocr Pract, 2017.
7. Davey M. Transdermal estrogen - a first-choice option in hormone therapy. Menopause Focus, 2014.
8. Mehta J, Kling JM and Manson JE. Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts. Front Endocrinol, 2021.