Hormone Replacement Therapy (HRT)

What is HRT?

Hormone replacement therapy refers to the replacement of one or more of the hormones estrogen, progesterone, and testosterone.

• Estrogen – The safest type of estrogen (and most commonly used in HRT) is 17 beta-estradiol. This has the same biological structure as the estrogen produced in the human ovary.

• Progesterone – This hormone is needed for all women who still have a womb to protect it from the effects of estrogen. One effect of estrogen is to thicken the lining of the uterus, which if unchecked can increase the risk of cancer. Using progestogen keeps the lining of the womb thin and prevents it from becoming abnormal.

• Testosterone – The levels of this hormone usually improve with adequate estrogen replacement. For women who continue to experience symptoms of low libido despite adequate replacement of estrogen, the addition of testosterone can be trialed.

Is HRT safe?

In a nutshell, for most women, the benefits of short-term HRT outweigh the risk, and the overall risks are small.

Is alcohol safe? Is Panadol safe? What about eating red meat? Even better than putting it into a safe or unsafe category, like many other choices we make, it is a nuanced decision. For HRT, it is the type of HRT, age when used, duration of use, along with personal and family risk factors that need to be considered.

What are the Risks?

• Breast Cancer:
  This is a concern that comes up frequently and is a major reason for the decline in the prescribing of HRT since the release of unfavourable reports from the Women's Health Initiative studies completed in 2002. However, the forms of HRT that are available and preferred now come with much lower risk.
  Breast cancer risk figures taken from studies in the UK show that there will be 13 cases of breast cancer per 1000 women (13/1000) within a 5-year period for women aged 50 who never used HRT.
  Using combined estrogen and progesterone HRT increases that number to 21 cases per 1000 women (21/1000). So, an extra 8 women. This number is thought to be lower with topical estrogen and is lower with estrogen-only HRT.
  How does it compare with other risk factors?

  • Drinking 2 units of alcohol per day increases the risk by 5 cases.

  • Sedentary lifestyle possibly increases the risk by 7 cases.

  • Drinking more than 3 units increases the risk by 27 cases.

  • BMI >30 is associated with an increased risk by 24 cases.

Recent studies show no increased risk if HRT is taken less than one year, and that risk declined after stopping HRT.

• Blood clots in the legs or lungs:
  Oral HRT is associated with an increased risk of 2 women per 1000 women (2/1000), lower than risks associated with being pregnant or taking a contraceptive pill.
  Again, topical applications are safer than oral tablets when it comes to the risk of venous thromboembolism.

• Stroke:
  A very minimal increase in stroke risk of 7 extra cases (3/1000) for oral treatment, again showing less/limited risk if topical rather than oral estrogen is used. Control of other risk factors, e.g., high blood pressure, also plays a role.

• Endometrial (womb lining) cancer:
  No increased risk is found if progesterone is used with estrogen.

• Heart disease:
  There can be an increased risk of heart disease with HRT use in the over 60 age group. Some studies suggest no increased risk and even a decreased risk, while others note a very increased overall risk.

• Gallstones:
  Increased risk of gallbladder disease is known, but the overall increase is low. For example, 1.1% of women need the gallbladder removed because of stones. In topical estrogen use, this number increased to 1.3%, and in oral estrogen, it is 2%.

What are the benefits of HRT?

HRT is the most successful way to treat menopausal symptoms and can transform how women transition through this stage of life.

Diet, exercise, antidepressants, or other medications, herbal remedies such as red clover and black cohosh, or "natural" hormones can be helpful but are not as effective at controlling symptoms such as hot flushes and night sweats.

The main benefit of HRT is to relieve symptoms:

Vasomotor symptoms of hot flashes, flushes, and night sweats can show improvement within days or weeks of starting.

Anxiety or low mood and sleep disturbance may take longer.

Vaginal dryness and discomfort during intercourse, recurrent urinary or vaginal infections are best treated with vaginal estrogen.

Other benefits include:

• Reduced risk of bone loss: Menopause is associated with a period of increased bone loss. HRT reduces this bone loss and the risk of osteoporosis and associated fractures. Though HRT should not be used primarily for this reason.

• Possibly reduced risk of cardiovascular disease: There is a lot of debate surrounding this. Menopause affects cholesterol levels, and cardiac risks for women rise to that of male counterparts after menopause. More research is being done to see if early use of HRT reduces the risk of cardiovascular disease.

• Possibly reduced future risk of type 2 diabetes, depression, and bowel cancer and protects against osteoarthritis.

What are the types of HRT?

In Hong Kong, there are oral and topical and vaginal options for HRT; there are no patches or sprays available.

• Preferentially, topical estrogen is considered the safest form of HRT; however, oral tablets can also be used. Oral tablets may be estrogen alone or in combination with progesterone.

• Progesterone is usually taken orally for symptom relief and endometrial protection; other options are considered "off-label" uses.

• The Mirena coil (IUD) is a way to maintain good contraceptive coverage and protect the lining of the uterus during estrogen use as it releases a progestogen into the uterus.

• Vaginal estrogen is excellent for reducing vaginal discomfort and dryness and can be used alongside the above methods. By itself, it cannot relieve other symptoms of perimenopause/menopause.

• Testosterone gel can be used off-label as an additional therapy when required.

• For women under 50 who still need contraceptive coverage, the combined pill, while not HRT, can be an option.

• Tibolone, a synthetic hormone with multiple effects, may be suitable for some women, especially those who are not able to use or tolerate regular HRT.

As you can see, there is an array of options that can be trialed to meet the needs of symptoms and life stage, with fine-tuning most women are able to find something that works best for them.

How do I know if I need HRT?

This is, of course, a personal choice as to whether or not a person starts HRT. Should you be considering using HRT for treatment, then a good time to start is when you experience symptoms that negatively impact your quality of life.

For some women, this may be when you are still having fairly regular periods (peri-menopause). The transitional time leading up to menopause is generally an average of about 4 years, and most women have more symptoms at the beginning rather than the end of this time period.

Resources

1. https://www.bmj.com/content/371/bmj.m3873

2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X/fulltext

3. https://pubmed.ncbi.nlm.nih.gov/28898378/

4. https://www.researchgate.net/publication/232225994_Effect_of_hormone_replacement_therapy_on_cardiovascular_events_in_recently_postmenopausal_women_Randomised_trial

5. https://www.tandfonline.com/doi/full/10.1080/13697137.2017.1421925

6. https://news.cancerresearchuk.org/2017/05/25/alcohol-and-breast-cancer-how-big-is-the-risk/

Against

1. https://pubmed.ncbi.nlm.nih.gov/36318127/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754905/#:~:text=Conclusion,women%20with%20intensive%20sports%20participation.