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Menopause, Hormone therapy and Breast cancer —-

Menopause is a period representing the end of a woman’s reproductive years. It is a natural phase in a woman’s life, where the menstrual cycle has ceased for at least 12 consecutive months. In simple words, it is a stage where you will no longer have your monthly period. The average age of reaching menopause ranges from late 40s to early 50s.

Stages of Menopause

Menopause occurs in three main stages including:

Perimenopause/menopause transition: This stage begins about 10 years prior to menopause, probably in the 40s. It is characterized by gradual decrease of estrogen production in the ovaries which is further accelerated in the final one to two years of the perimenopause phase.

Menopause: This is a stage where the ovaries stop major production of estrogen and no longer release eggs, leading to cessation of menstrual periods.

Postmenopause: This is the stage after menopause has occurred, where a woman has no longer experienced menstrual bleeding for one entire year.

Symptoms of Menopause

Although every woman’s experience of menopause may be different, some common symptoms during different phases of menopause include:

1. Hot flashes and night sweats
2. Irregular menstrual cycles
3. Varying levels of menstrual bleeding
4. Emotional changes and mood swings
5. Vaginal dryness
6. Tenderness/soreness of breasts
7. Headaches
8. Anxiety and depression
9. Abnormal weight gain
10. Increased hair growth on different parts of the body
11. Thinning/loss of hair on scalp.

Menopausal hormone therapy

Menopausal hormone therapy (MHT), also known as postmenopausal hormone therapy and hormone replacement therapy is a treatment method used in the management of menopausal symptoms. It involves treatment with low doses of hormones such as estrogen and progesterone.

There are two main types of menopausal hormonal therapies:

1. Estrogen therapy (ET): This is a hormone therapy which only includes administration of estrogen alone to provide symptomatic relief from menopause. This is generally indicated in women who have undergone hysterectomy and do not have a uterus.
2. Estrogen plus Progestin Therapy (EPT): This is a hormone therapy which includes administration of progestin along with estrogen. It is indicated in women who have a uterus (have not undergone hysterectomy) to protect them from endometrial cancer. This is because, using estrogen alone is linked to an increased risk of endometrial cancer.

Different formulations and routes of administration of MHT

Hormone replacement therapies for menopause can be administered both systemically and topically based on the symptoms and different formulations. They are available in the form of oral tablets, skin patches and injections for systemic administration. Topical formulations are available as gels, sprays or creams for localized symptoms such as vaginal dryness. Based on the type of symptoms and severity, your doctor will decide the appropriate method of administration.

General health benefits and risks of MHT

Studies have shown that although MHT is associated with certain health benefits along with relief from menopausal symptoms, it also poses certain risks to woman’s health. Let us take a look at some of the benefits and risks of MHT:

Benefits

1. Maintains bone health: Women in their menopausal stages experience hormonal changes which have direct effects on bone density. Estrogen is an essential hormone required for maintaining bone health. Studies have shown that hormone therapy, either ET or EPT have reduced the risk of osteoporosis along with decreased hip and vertebral fractures in women.
2. Menopausal symptom relief: The gradual decrease of hormone levels during menopausal stages leads to troublesome symptoms such as hot flashes, night sweats, vaginal dryness, etc. all of which are relieved with MHT.
3. Other health benefits: MHT decreases the risk of colon cancer and diabetes, improves overall mental well-being in women and has shown lower death rates for women taking MHT in their 50s.

Risks

1. Endometrial cancer: Women who have not undergone hysterectomy and still have their uterus intact are at a higher risk of developing endometrial cancer if they are on ET alone without the use of progestin.
2. Dementia: According to studies, women aged 65 years and above are at a higher risk of developing dementia with either estrogen therapy or estrogen plus progestin therapy.
3. Blood clots, stroke, and heart attack: Studies have shown an increased risk of clots, stroke and heart attack in women taking estrogen therapy alone or a combination hormone therapy with estrogen and progestin. However, lower risk rates were observed once the medication was stopped.
4. Gall bladder/gallstone problems: Women on MHT are also at a higher risk of developing gallbladder-related problems.

Menopausal hormone therapy and risk of Breast Cancer

There are specific breast cancer risks associated with the long-term usage of hormonal therapies. Several randomized controlled trials and observational studies have determined the link between MHT and breast cancer. The studies concluded the following:

1. Women treated with a combination therapy of estrogen plus progestin had higher chances of being diagnosed with breast cancer.
2. Breast cancers in these women appeared to be larger and were likely to spread to the lymph nodes before being diagnosed.
3. Estrogen therapy alone and estrogen plus progestin therapy interfered with mammography for early detection of breast cancer.
4. Women on MHT required repeated mammograms to confirm if the suspected breast abnormalities were actually cancer.
5. The risk of breast cancer increased with prolonged usage of MHT and decreased with cessation of MHT.
6. Women who were on EPT (combination therapy) were associated with increased dense breast tissue, which is a notable risk factor for breast cancer.
7. Increased mammographic density following the first year of EPT in women accounted for complete increase in breast cancer risk.
8. The number of deaths due to breast cancer were observed to be higher in women who had taken EPT (combination) therapy.
9. MHT may increase tumor growth in women previously diagnosed with breast cancer, hence it is not recommended in such cases.

The U.S Food and Drug Administration (USFDA) recommends usage of MHT with the lowest possible doses for the shortest period of time to relieve menopausal symptoms and minimize the associated risks of MHT. It is important for women to discuss about various factors such as age, associated risks, benefits and available treatment options with their healthcare providers before making a decision on MHT.  

References:

1. Menopause, Perimenopause and Postmenopause. Cleveland Clinic.
   https://my.clevelandclinic.org/health/diseases/15224-menopause-perimenopause-and-postmenopause
   Accessed on 26 August, 2021.
2. Menopausal Hormone Therapy and Cancer. National Cancer Institute.
   https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/mht-fact-sheet#r2
   Accessed on 26 August, 2021.
3. Hormone replacement therapy (HRT) and menopause. Better Health Channel.
   https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/hormone-replacement-therapy-hrt-and-menopause#menopause-symptoms-and-hrt
   Accessed on 26 August, 2021.
4. Hormone Therapy for Menopause Symptoms. Cleveland Clinic.
   https://my.clevelandclinic.org/health/treatments/15245-hormone-therapy-for-menopause-symptoms
   Accessed on 26 August, 2021.
5. Oliver-Williams C, Glisic M, Shahzad S et al. The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review. Hum Reprod Update. (2018); 25(2):257-271.
   Accessed on 26 August, 2021.
6. Hormone Therapy: Benefits & Risks. The North American Menopause Society (NAMS).
   https://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-treatments/hormone-therapy-benefits-risks
   Accessed on 26 August, 2021.
7. Menopausal Hormone Therapy and Cancer Risk. American Cancer Society.
   https://www.cancer.org/cancer/cancer-causes/medical-treatments/menopausal-hormone-replacement-therapy-and-cancer-risk.html
   Accessed on 26 August, 2021.
8. Menopausal Hormone Therapy After Breast Cancer. American Cancer Society.
   https://www.cancer.org/cancer/breast-cancer/living-as-a-breast-cancer-survivor/menopausal-hormone-therapy-after-breast-cancer.html
   Accessed on 26 August, 2021.
9. Using HRT (Hormone Replacement Therapy). Breastcancer.org
   https://www.breastcancer.org/risk/factors/hrt
   Accessed on 26 August, 2021.
10. Chi L, Noel S, Polly N Hormone Replacement Therapy in Relation to Breast Cancer. JAMA. (2002) ;287(6):734-741.
    Accessed on 26 August, 2021.
11. Long-Term Follow-Up Suggests Estrogen-Only and Combination Hormone Replacement Therapy Have Opposite Effects on Breast Cancer Risk. Breastcancer.org
    https://www.breastcancer.org/research-news/hrt-and-its-effect-on-bc-risk
    Accessed on 26 August, 2021.
12. Jones, M., Schoemaker, M., Wright, L. et al. Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? Br J Cancer (2016); 115, 607–615.
    Accessed on 26 August, 2021.
13. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. (2020) :m3876.
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14. Breast cancer and menopausal symptoms. Cancer Research, UK.
    https://www.cancerresearchuk.org/about-cancer/breast-cancer/living-with/menopausal-symptoms
    Accessed on 26 August, 2021.

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