HRT doses explained

What you need to know about hormone replacement during the perimenopause and menopause

Hormone replacement therapy (HRT) is usually the first-line treatment to improve symptoms of the perimenopause and menopause [1]. It works by topping up or replacing your missing hormones.

All types of HRT will usually contain estrogen, progesterone if you have a uterus and sometimes testosterone.

But what are these hormones, why are there different doses and why do absorption rates vary from person to person?

This article tackles these key questions and more.

What is estrogen and what do I need it for?

Estrogen is a hormone produced predominantly by your ovaries with small amounts coming from your adrenal glands. It helps to regulate your menstrual cycle and the development of female characteristics during pregnancy, such as breasts.

It also plays important roles in bone health, memory and cognition and cardiovascular health and is essential for many bodily functions, including:

• temperature regulation
• maintaining healthy and strong muscles and joints
• helping your nerves work correctly
• maintaining a healthy metabolism
• improving the way your immune cells work and function
• reducing inflammation throughout your body
• improving the way other neurotransmitters (such as serotonin) work in your brain
• keeping the lining of your vagina and vulval tissues healthy and lubricated

Estrogen is actually an umbrella term for three types: estradiol, estrone and estriol. Estradiol is the main type of estrogen produced by your body in your reproductive years.

You have estrogen receptors in cells throughout your entire body, so when levels fluctuate and fall, this can trigger wide-ranging and varying symptoms including low mood, anxiety, memory problems, poor sleep, joint aches and pains, brain fog, hot flushes and vaginal dryness.

How is estrogen given in HRT?

All HRT regimes will usually include estrogen, plus progesterone if you still have your uterus, and sometimes testosterone.

Estrogen can be given either through your skin, known as transdermal estrogen, or orally in the form of a tablet.

Transdermal estrogen can be given in the form of

• gel
• patches
• spray

Transdermal HRT is absorbed directly through your skin into your bloodstream. This means that it bypasses your liver and causes less side effects. In addition, your liver produces clotting factors, which means that if a tablet of estrogen is taken, there is a small increased risk of a blood clot occurring. There is no risk of clot for women who use transdermal estrogen.

Transdermal estrogen can also be taken by women who suffer from migraines (women with migraine should not take estrogen in tablet form) and women who have had a clot in the past.

Another benefit of transdermal estrogen is that doses can be altered more easily, allowing you to be treated individually and have your HRT dose and type tailored to your symptoms.

What is HRT made from?

In the past, estrogen was only given as a tablet which was derived from pregnant horses’ urine.

However the majority of estrogen and progesterone in the HRT that is now prescribed is derived from yam plants. When hormones have the same molecular shape as the hormones your body naturally produces itself, they are called body identical hormones.

This form of estrogen most commonly used is called 17-β estradiol. All types of transdermal estrogen contain this type of estrogen.

The brand of progesterone most commonly used is Utrogestan which is another body identical hormone derived from yam plants. There are some other brands of body identical versions of progesterone available. Sometimes, synthetic versions of this hormone are used which are called progestogens. This will be discussed in more detail below.

Body identical testosterone is also derived from yam plants.

I’ve started taking HRT. How will I know how much estrogen I need?

A consensus statement by the British Menopause Society states that HRT dosage, regimen and duration should be individualised, with annual evaluation of advantages and disadvantages [2].

We prescribe doses according to symptoms and some women have more symptomatic improvement with higher doses than other women. Prescribing HRT at the right dose improves symptoms and also reduces future risk of heart disease, osteoporosis, clinical depression and type 2 diabetes.

Hormone blood tests are not usually needed to make a diagnosis of the perimenopause or menopause, as they are unreliable especially as the levels fluctuate so much during the perimenopause. However hormone blood tests can be useful for some women to monitor the absorption of hormones from your HRT.

As your hormone levels vary from day to day, it’s always important to consider the whole picture, taking into account how you feel and if your symptoms have changed since starting to take HRT and this information will be considered to help decide if you need a change in your dose or type of HRT.

Estradiol levels are most useful for monitoring how well a type of HRT is being absorbed. They are not that accurate if you take estrogen as a tablet, as the estrogen becomes metabolised into different types of estrogen when it is digested. However, they can be helpful if you take transdermal HRT to confirm if it is being adequately absorbed through your skin into your bloodstream, especially if you are still experiencing symptoms. If you are having symptoms despite taking HRT, then it may be that there are other causes for your symptoms so it is always important to discuss any symptoms with a healthcare professional.

Generally, to offer the health benefits of estrogen replacement, estradiol blood levels need to be over 250pmol/l. Few women need to have a level above 1000pmol/l. Levels can really alter rapidly during the perimenopause and it can be common for women to transiently have higher levels.

This is the usual range of estrogen when you are menstruating. In comparison, during pregnancy levels of estrogen can be around 65,000pmol/l.

However, the dose of estrogen needed to relieve the symptoms of the perimenopause and menopause can really vary between people.

Studies have shown that younger women experiencing symptoms of the perimenopause or menopause often tend to need higher levels of estradiol (and therefore usually higher doses of HRT) than older women do.

It is important to have adequate estrogen to improve symptoms as well as to improve future health. If amounts of estrogen are too low then it is likely you will experience symptoms and also the health risks of the menopause (such as increased risk of heart disease, osteoporosis, clinical depression and dementia) will still be present.

My friend is on a lower dose than I am. Does that mean my dose is too high?

Some women need higher doses than other women to achieve the same benefits, especially as estrogen can often be absorbed differently through the skin.  For example, some people find they absorb estrogen much more effectively through gels rather than patches, whereas for other women they find they absorb more effectively using patches compared to gels. Other people find they absorb some brands of gels or patches better than others, despite them all containing the same type and dose of estradiol.

Because of this, to achieve a specific estradiol level, some women may only need a very low dose and some may need a higher dose.

Is it safe to use a higher than licensed dose of estrogen?

There is no current maximum licensed dose of estrogen in the British National Formulary (BNF). The BNF states that doses of estradiol should be adjusted according to response.

Some women need higher doses to achieve a physiological level of oestradiol. It is more common that younger women with premature ovarian insufficiency (menopause before the age of 40) need higher doses to achieve a physiological response.

While many women will respond well to lower doses of estrogen, some will require higher doses such as 200mcg or 300mcg of estradiol patches to provide adequate symptom control.

Why do some people absorb female hormones differently to others?

There are so many reasons why you may absorb hormones through your skin differently to others.

There are many tiny blood vessels, called capillaries, which supply blood and nutrients to your skin and also absorb the hormones from the patches or gels. The depth and numbers of these capillaries varies between women [3].

Other factors that affect absorption of hormones through your skin into your body will be the thickness of the layers of your skin, how well hydrated it is and also the temperature of your skin. The fact the skin works as a barrier is relevant too and some people’s barriers will be better than others even to hormones in patches and gels that are designed to penetrate your skin [4].

In addition, there are many proteins and enzymes that help make up the five layers of your skin. These enzymes can affect the amount of hormones that are available in your bodies (bio-availability) from the patches and gels and there is evidence this composition of proteins and enzymes alters with time too [5].

Some studies have found that your ethnicity can affect how much of a drug is absorbed through your skin. One study found people from a Hispanic background had the best absorption rate, followed by White people, Asian people and people from an Afro-Caribbean background [6].

In summary, there are many different factors affect the dose of estradiol you need to ensure you have adequate estrogen for your perimenopause or menopause. You should talk to a healthcare professional if you feel your dose or type of HRT needs changing.

Progesterone doses

If you still have your uterus (womb), taking estrogen can cause the lining (endometrium) to thicken. To prevent this thickening, you will be required to take either body identical progesterone (Utrogestan, Cyclogest or Lutigest) or a synthetic progestogen tablet or have the Mirena coil.

The regime in which you take your progesterone will depend on the type and whether you are still having periods or not. If you are still having periods, the usual recommended dose is 200mg Utrogestan every evening for two out of four weeks. Once periods have stopped, the dose of Utrogestan is usually 100mg every evening. If you experience progesterone intolerance symptoms (such as low mood), the capsules or an alternative progesterone can often be used vaginally.

The dose of progesterone needed does not always depend on your dose of estrogen. There is no strong evidence to suggest that if you are prescribed a higher dose of estrogen that you also require a higher dose of progesterone. Some women are prescribed a higher dose as they absorb estrogen through their skin less easily than other women who are prescribed lower doses. Other women need higher doses to improve their symptoms.

If you are experiencing bleeding when you shouldn’t be bleeding, regardless of your dose of estrogen, you should discuss this with your healthcare provider to see if any other investigations are needed. Bleeding commonly occurs in the first 3-6 months after starting or altering the dose of HRT and can occur with both higher and lower doses of estrogen. Sometimes a higher dose of progesterone is recommended to improve any bleeding.

A recent audit of patients at Newson Health found that abnormal vaginal bleeding occurs in fewer than 1% of our patients. Moreover, there was no correlation between oestradiol dose levels and the incidence of problem bleeding.

Testosterone doses

When commencing testosterone replacement, the starting dose is usually 5mg of cream or gel daily. Generally, after 3-6 months a blood test is done to check the level of testosterone and often also your sex hormone binding globulin (SHBG) to determine your Free Androgen Index (FAI).

If your levels are low despite treatment with testosterone and you are still experiencing symptoms of testosterone deficiency (reduced libido, low energy, reduced motivation) then you may be recommended to increase the amount of testosterone gel or cream you are using and then repeat the blood test again after a few months.

Side effects due to testosterone are very rare if levels of testosterone and Free Androgen Index remain in the female range.

Seeking support and care from a healthcare professional

If you need menopause treatment advice, seek help from your healthcare professional or book an appointment with Newson Health.

Newson Health offers evidence-based treatment and care for women going through the perimenopause and menopause. With clinics nationwide we offer in-person and virtual consultations. We are also able to see patients who reside outside the UK following a first appointment either face-to-face in one of our clinics or virtually while in the UK.* All follow-up consultations can then be held virtually in the country you resided in.

Our team of menopause specialist doctors, nurses and pharmacists will take time to listen to you, discuss your symptoms and offer a comprehensive treatment plan, tailored to your needs and preferences.

Use the button below to find out more and book your appointment.

*This doesn’t currently apply to residents of the US and Canada. All medication will need to be sent to a UK postal address; this includes PO Box addresses.

References

1. NICE (2015) ‘Menopause: diagnosis and management’, www.nice.org.uk/guidance/ng23
2. British Menopause Society (2020), ‘BMS & WHC’s 2020 recommendations on hormone replacement therapy in menopausal women’
3. Tinhofer I.E., Zaussinger M., Geyer S.H., Meng S., Kamolz L.P., Tzou C.H., Weninger W.J. (2018), ‘The dermal arteries in the cutaneous angiosome of the descending genicular artery’, J Anat, 232(6) pp.979-86. doi: 10.1111/joa.12792.
4. Singh I., Morris A.P. (2011), ‘Performance of transdermal therapeutic systems: effects of biological factors’, Int J Pharm Investig, 1(1):4-9. doi: 10.4103/2230-973X.76721.
5. Liu, P., Higuchi, W.I., Ghanem, A.H., Good, W.R. (1994), ‘Transport of beta-estradiol in freshly excised human skin in vitro: diffusion and metabolism in each skin layer’, Pharmaceutical Research, 11(12), pp.1777–84. doi.org/10.1023/a:1018975602818
6. Leopold C.S, Maibach H.I, (1996), Effect of lipophilic vehicles on in vivo skin penetration of methyl nicotinate in different races, International Journal of Pharmaceutics, 139, 1–2, pp.161-67, doi.org/10.1016/0378-5173(96)04562-0.