HRT for women: Menopause Hormone Therapy

Menopause hormone therapy – MHT (also known as hormone replacement therapy – HRT) is the use of hormones during the perimenopause to alleviate symptoms such as hot flashes, vaginal dryness, and cognitive and mood symptoms. HRT for women during perimenopause can significantly improve quality of life and sleep and reduce symptoms.

What is perimenopause?

Perimenopause is the time of life approaching and after menopause when your ovaries are slowly starting to make less estrogen and progesterone. You might have some perimenopausal symptoms during this time. It takes several years and usually happens between the ages of 45 and 55 years.

What is menopause?

Menopause is the time in a woman’s life when her period stops. It usually happens around age 51, but it can happen earlier or later. Once you’ve gone 12 months since your final menstrual period, you’re considered to be in menopause.

Symptoms of Perimenopause

The most common symptom of perimenopause is irregular periods. Your periods can also become heavier or lighter than usual, and they may come more or less often than every 28 days. You may also have any (or all) of the following symptoms:

• Hot flashes
• Night sweats
• Sleep problems
• Mood changes
• Weight gain
• Vaginal dryness
• Thinning hair
• Reduced sex drive

While these symptoms may be mild and managed with lifestyle changes such as; a eating whole foods, stress management or sleep modifications for some women, others experience severe and debilitating symptoms. For those who have difficult symptoms, especially symptoms that are negatively affecting your quality of life, menopause hormonal therapy can be life-changing.

What is Menopause hormone therapy?

Hormone therapy is the most effective treatment available for menopausal symptoms, especially for moderate to severe symptoms. It involves taking a daily supplement of either estrogen alone, or a combination of estrogen and progesterone. The pill (oral) form of hormone therapy is the most common, but you can also get it in the form of a patch, gel, or vaginal ring.

Benefits of hormone replacement therapy

There are many potential benefits to taking hormone therapy, including relief from menopausal symptoms like hot flashes and night sweats, as well as protection from osteoporosis and heart disease.

• Menopause hormone therapy (MHT) reduces the severity and frequency of hot flashes by 85% and is the most effective treatment for this symptom.
• MHT reduces vaginal dryness and therefore can improve pleasure during sex.
• MHT can improve sleep and quality of life by reducing hot flashes.
• MHT reduces the risk of post-menopausal bone fractures, including hip fractures.
• MHT is not associated with weight gain.

HRT risks

There are also some risks associated with hormone therapy, particularly when it comes to breast cancer and blood clots. Before starting hormone therapy, it’s important to talk to your doctor about the potential risks and benefits.

Making the decision to take hormone therapy is a personal one, and there’s no right or wrong answer. Ultimately, you’ll need to weigh the risks and benefits for yourself and decide what’s best for you.

Estrogen alone stimulates growth of some body tissues including breast and endometrium. This is why it is advised to use in combination with progesterone.

Minimizing the risks of menopausal hormone therapy

• Be breast aware, have regular breast checks and screening mammograms
• MHT should be reviewed annually in consultation with your doctor.
• Personal benefits versus risk should be discussed.
• Oral MHT increases the risk of venous thromboembolism (VTE). The risk is less with the use of transdermal preparations and also with the use of micronized progesterone rather than synthetic progestins.
• See your doctors if you have unusual vaginal bleeding, breast changes or shortness of breath or leg swelling

HRT options

The two main sex hormones in women are estradiol and progesterone. In the uterus estrogen stimulates growth of the endometrium and progesterone stimulates differentiation of the cells and glands to secrete substances to make ready for a pregnancy. These hormones can be either body identical hormones or synthetic or non-identical hormones. They also can be delivered into the body in a variety of methods.

Estrogens

Estrogens come in tablets, gels, patches and vaginal rings. These products contain different kinds of estrogen (estradiol, conjugated equine estrogen or estriol) which are all effective in treating menopausal symptoms. Estradiol is a body identical estrogen – meaning it is identical to the main estrogen produced in the ovaries.

As oral estrogen is absorbed it passes directly to the liver and can elevate triglyceride levels and blood pressure. It can also increase the risk of clotting.

If you have any of the following conditions, you should avoid oral estradiol and should instead use hormone replacement patches or gel:

• metabolic syndrome,
• increased BMI,
• high blood pressure,
• smoker or vaping
• risk of deep vein thrombosis or clots in the lung
• risk of heart attack or stroke
• or any woman wishing to minimize the risks of the above conditions.

Estrogen-only menopausal hormone therapy is sometimes prescribed in women who have had a prior hysterectomy.

Estrogen vaginal cream is sometimes used without progesterone in women whose only symptom is vaginal dryness.

Estrogen is prescribed in combination with progesterone in women with a uterus.

For women wanting natural estrogen replacement, using a therapy that contains estradiol is important.

The estrogen dose depends upon how a woman’s symptoms respond and on her well-being rather than blood levels.

Progestogens for menopausal hormone therapy

Both natural progesterone and synthetic preparations – known as synthetic progestins act on the progesterone receptor.

Synthetic Progestins

Synthetic progestins are molecules that are similar but not identical to the progesterone your ovaries produce. They are either modified progesterone or other steroid hormones such as testosterone. Most synthetic progestins have other biological effects, acting on the androgen receptor, glucocorticoid receptor or mineralocorticoid receptors. This can produce unwanted side effects and adverse health risks.

Common oral synthetic progestins includes:

• medroxyprogesterone acetate
• norethisterone
• levonorgestrel

An alternate method of delivering a synthetic progestin is via an intra-uterine device such as Mirena (licensed for 5 years) or Jaydess (licensed for 3 years). As they deliver the progestin locally to the endometrium the levels delivered are much lower than required via an oral tablet.

• Mirena releases 20 microgram/24 hours of levonorgestrel initially, reducing to 18 microgram/24 hours after 1 year and to 10 microgram/24 hours after five years.
• Jaydess releases 14 µg/24 hours of levonorgestrel after 24 days and is reduced to approximately 10 µg/24 hours after 60 days. It then declines to 6 µg/24 hours after one year and 5 µg/24 hours after three years.

Tibolone is a synthetic progestogenic hormone which, once metabolized, also has estrogenic, progestogenic and testosterone effects that is used for hormone replacement therapy in perimenopausal women.

Natural Progesterone: micronized progesterone

Oral micronized progesterone is a body identical hormone. It is metabolized in the same pathways as progesterone that is made by your ovaries. It is metabolized to allopregnanolone which is a calming neurosteroid, which can help with sleep.

If your preference is to use natural or body identical menopause hormone therapy then oral micronized progesterone is the best progestogen for you.

Progesterone cannot be absorbed through the skin in sufficient amounts to provide protection to the endometrium which is why progesterone is not recommended as a hormone replacement patch or cream.

Body Identical HRT

Body identical hormone replacement therapy utilizes hormones that are identical in molecular structure to the hormones your own body makes.

Typically estradiol is used as the estrogen and micronized progesterone is used as the progesterone.

Combined HRT: Estrogen with progesterone

In a woman with a uterus, estrogen hormone therapy alone, i.e. unopposed estrogen therapy increases the risk of endometrial hyperplasia and cancer, because estrogen stimulates cell growth – acting as a hormonal growth factor. These women need combination hormone therapy with both estrogen and progesterone to protect their endometrium.

Combined hormone replacement therapy can be given cyclically or continuously.

Cyclical combined HRT

• Estrogen is given daily
• Progestogen is given for 10-14 days of the month
• Women using cyclical combined HRT will have a monthly withdrawal bleed
• It is usually used in the early stages of perimenopause when women are still having periods.

Continuous combined HRT

• Both estrogen and progestogen are given daily.
• Continuous combined hormone therapy should not produce a monthly bleed.
• This is the usual type of hormone therapy given once women have experienced menopause (i.e. they are no longer having natural periods).
• If continuous hormone replacement therapy is commenced prior to menopause breakthrough bleeding can occur.

HRT  side effects

Common side-effects with estrogen only hormone therapy include:

• breast enlargement and tenderness,
• nausea,
• exacerbation of hormonally-sensitive migraine headache.

Risks of menopause hormone therapy: Estrogen Only Hormone Therapy

Estrogen-only HRT for women does have a number of risks. It is important to understand these and talk to your doctor about them.

Oral estrogen increases the risk of blood clots (venous thromboembolism).

The risk increases with age and other risk factors such as:

• obesity,
• previous thromboembolism (blood clot),
• smoking
• immobility.

In healthy women younger than 60 years, the risk with oral estrogen alone is 3 per 10,000 per year.

Oral estrogen increases the risk of stroke which increases with age.

Stroke risk is not significantly increased in women younger than 60 years with normal blood pressure. The risk may be lower with lower doses and the use of transdermal estrogen.

Oral estrogen is associated with an increased risk of gallbladder inflammation (cholecystitis).

Estrogen alone has not been shown to increase breast cancer risk

This comes from data from both randomized controlled trials (Anderson 2012) and a large observational study did not show an increase in breast cancer rates in women who used estrogen only therapy for 20 years (Chen 2006).

Estrogen alone and heart disease

Estrogen only hormone therapy commenced within 10 years of the final period (menopause) does not increase the risk of coronary heart disease and may decrease the risk (Boardman 2009).

Risks of menopause hormone therapy: Combined Hormone Therapy

These are the risks that combined HRT for women poses. It is important to understand these and talk to your doctor about them.

HRT and Breast cancer

There is an increasing body of data comparing synthetic vs body identical progestogen use demonstrates that while synthetic progestin use increases the risk of breast cancer, and testosterone-derived progestins increase the risk higher. The data also shows that micronized progesterone is either breast cancer neutral or reduces the risk of breast cancer below baseline risk if never used menopause hormone therapy.

A study from France that followed up 80,377 postmenopausal women for an average of 8.1 years suggests that there is an increased risk of breast cancer in women who use estrogen + synthetic progestin but not in women who use estrogen + micronized progesterone (Fournier 2008).

A further French study showed that combined estrogen-progestogen hormone therapy containing a synthetic progestin, had an increased risk ratio of 1.57 for progesterone-derived progestins (medroxyprogesterone acetate) and 3.35 for testosterone-derived progestins (norethisterone). 

This study also found that Tibolone use was also associated with an increased risk of breast cancer  (Cordina-Duverger 2013).  

A meta-analysis of studies of postmenopausal women using estrogen with either natural progesterone or synthetic progestins, found that estrogen + progesterone was associated with a lower risk of breast cancer compared with estrogen + synthetic progestins (relative risk 0.67) (Asi 2016).

The Lancet meta-analysis in 2019 found that the relative risk for use of estrogen + micronized natural progesterone for less than 5 years was 0.91, i.e. 9% lower risk in users of micronized progesterone than for never-users of HRT. This was not published in the main body of the text but shown in their appendix (Collaborative Group on Hormonal Factors in Breast Cancer 2019).

HRT and endometrial cancer

Estrogen menopausal hormone therapy without progestogen increases the risk of endometrial cancer in women with a uterus. Using a combination hormone therapy of estrogen with progesterone is essential to reduce the risk of endometrial cancer in women with a uterus. Micronized progesterone needs to be adequately dosed to ensure endometrial protection.

Irregular or breakthrough bleeding that persists beyond 6 month of initiating hormone replacement therapy should be investigated.

HRT and stroke

Oral MHT increases the risk of stroke and the risk increases with age. Stroke risk is not significantly altered in women younger than 60 years with normal blood pressure. The risk is thought to be less with the use of estrogen gel or skin patches rather than with oral estrogen but further research will hopefully give definitive answers regarding this.

HRT and heart attacks and strokes

Stopping menopausal hormone therapy increases the risk of heart attacks and strokes.

HRT and bone health

Stopping menopausal hormone therapy increases the risk of fractures.

Frequently Asked Questions about Menopause Hormone Therapy

Is hormone replacement therapy necessary?

No. Some women get through perimenopause without using any HRT. Some women use herbs or supplements to support their hormones and mood during perimenopause and this is sufficient. Other women find that self-care through food, exercise, connection lowering stress and sleeping well helps them flourish during perimenopause.

The symptoms and experience of perimenopause is unique to each woman and if hormone therapy sounds like it would be helpful for you, speak with your doctor.

What should I expect when I go to see my doctor about menopause hormone therapy?

• Your doctor will take a history and clinical examination to determine safety and risks of MHT for you.
• Check your mammograms and cervical screening is up to date.
• Discuss with you the benefits and risks and various options.
• See your doctor if you have any unexplained vaginal bleeding.

Should I still take HRT after menopause?

Perimenopausal symptoms can often continue for a number of years after the periods have ceased. Many women continue to use HRT until their symptoms have settled. An annual review with your doctor will provide you with the opportunity to discuss how your therapy is going and when to consider reducing or stopping HRT.

Can I take natural hormone replacement therapy after hysterectomy

Yes, after a hysterectomy you can take estrogen only therapy. If you are wanting a natural option then body identical estradiol is a good option for you.

Is progesterone and progestin the same thing?

Progesterone and progestins are not the same thing.

Micronized progesterone is a body identical hormone. It is the same progesterone molecule produced by your own ovaries and therefore is metabolized by same metabolic pathways as it is degraded by the body. Importantly progesterone is metabolized to allopregnenalone a neurosteroid by the liver, this has a calming effect on the brain.

Progestins are not body identical hormones. They are not metabolized in the same metabolic pathways as progesterone is by the body.

Micronized progesterone is a safer option in terms of breast cancer risks than synthetic progestins (Lewis 2019).

Menopause hormone therapy can be life-changing for women with perimenopause symptoms that do not improve with lifestyle changes, herbs or supplement support. Talk to your doctor to collaborate on which option will be best for you.

By Dr Deborah Brunt. Last reviewed 06/02/22.

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References

For a detailed overview see:

North American Menopause Society Position statement on hormone therapy 2017.

Australasian Menopause Society: Oestrogen Only Menopausal Hormone Therapy

Australasian Menopause Society:Combined Menopausal Hormone Therapy (MHT)

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476-486. doi:10.1016/S1470-2045(12)70075-X

Asi N, Mohammed K, Haydour Q, et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016;5(1):121. Published 2016 Jul 26. doi:10.1186/s13643-016-0294-5

Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2015;(3):CD002229. Published 2015 Mar 10. doi:10.1002/14651858.CD002229.pub4

Chen WY, Manson JE, Hankinson SE, et al. Unopposed Estrogen Therapy and the Risk of Invasive Breast Cancer. Arch Intern Med. 2006;166(9):1027–1032. doi:10.1001/archinte.166.9.1027

Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168. doi:10.1016/S0140-6736(19)31709-X

Cordina-Duverger E, Truong T, Anger A. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Systematic Reviews, 2016; 5:121; DOI 10.1186/s13643-016-0294-5

Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study [published correction appears in Breast Cancer Res Treat. 2008 Jan;107(2):307-8]. Breast Cancer Res Treat. 2008;107(1):103-111. doi:10.1007/s10549-007-9523-x

Lewis PJ. Rapid response to: HRT and breast cancer risk. BMJ 2019;367:l5928