This is a very important question as the route of entry into the body in itself can be connected to an increase or decrease in the risk of developing breast cancer.
So, in this article I will address the different routes, the different types of HRT, how to get the HRT, how much to take and how long to use it. Though before I do this, I think it is important to address the types of Estrogens and Progestogens, so you know what to look for and also what the term bio-identical means.
3 types of Estrogens
Estrone – E1 – predominantly produced in fat cells, a relatively lazy hormone primarily a storage hormone, which converts into E2. This hormone is the dominant Estrogen after menopause
Estradiol – E2 – predominantly produced in the ovaries is a very powerful hormone, which is mass produced from puberty to menopause, responsible for the female characteristics, aka changing you from a princess to a queen . E2 is also produced in fats and skin cells, the Adrenals, bone and brain
Estriol – E3 predominantly produced in the placenta, liver and gut functions as a mini E2, but is 100 times less powerful.
E1 and E2 are broken down in the liver to water-soluble molecules to be excreted.
In the process of making E1 and E2 water-soluble the liver makes 6 ‘new’ Estrogens, 2 of which can create DNA damage and mutations connected with breast cancer. I call these the “naughty” Estrogens
E3 is one of the ‘new’ liver Estrogens though not one of the ‘naughty’ Estrogens. It is made from E2 and studies show that E3 has many positive effects and may therefore be the safer choice for HRT.
In Europe the Estrogens used in HRT are mostly bio-identical with the Estradiol and Estriol produced by the body. Remember if the name on the label is Estradiol or Estriol then the hormone is bio-identical.
If the product contains other names such as conjugated equine estrogens (CEEs), which is a collection of horse Estrogens then the hormone is not bio-identical.
Progesterone – P4 – is the body’s natural Progestogen and is predominantly produced by the corpus luteum after ovulation and in the Adrenals.
Progestins – are synthetically produced Progestogens and should not be confused with Progesterone.
These hormones have similar actions to Progesterone but are not identical in their molecular makeup.
This means that they can create side effects and/or lack some of Progesterone’s abilities to protect against the effects of Estrogen, which could result in cancers and blood clots, etc. as this study from 2005 clearly demonstrates
The names Progestogen, Progesterone and Progestin are used simultaneously by the medical world even though there is a major difference in their biochemical structure and function. This can result in some GPs referring to all of these hormones as Progesterone.
You’re probably thinking why are Progestins still being used when they clearly have some downfalls.
The reason lies with Progesterone; as a supplement it is not completely reliable.
Progesterone is responsible for protecting tissue against the actions of Estrogen.
Related to the uterine wall / the endometrium Progesterone prevents/controls the Estrogenic actions of creating blood and the thickening of the wall.
Progesterone as supplements/medication is quickly metabolised (broken-down) in the liver, quicker than Estrogen and thereby can result in unstable protection when used together with Estrogen in HRT.
Progestins on the other hand are broken down more slowly and thereby offer continuous protection to the uterine wall, but because they are not bio-identical with Progesterone can in themselves create problems.
The standard medical recommendation is ‘never use Estrogen therapy without a Progestogen, but this advice is based on older studies where Estradiol / E2, in pill form and often in large doses was used.
What if Estriol / E3 is used?
Do we need a Progestogen?
Possibly not, but don’t guess – check
Regular Uterine ultra sound scans will clearly show if there is a thickening of the wall and therefore the need for Progestogen protection. At the same time a scan will check the ovarian area for possible tumour growth.
Hormone Delivery Systems
Orally – Pills
Swallowing pills is the oldest HRT route (Estrogen pills have been prescribed since 1942) and medically until quite recently the most popular route.
Most of the HRT studies are based on the pill form.
Pills can be Estradiol / E2 or a combination of E2 with a Progestin
The downside of oral administration is that absorption is affected by the variables of how the digestive system and the liver are working from hour to hour.
Very important is that the first stop is the liver where Estrogen is metabolised. And as some of the Estrogen in the pill will be excreted higher doses are necessary, even an increased frequency of taking the pills, such as twice a day to ensure some of it coming back into circulation to achieve the desired effects.
All in all, your liver may be subjected to very high levels of Estrogen to metabolise, which can increase the risk of creating the liver Estrogens that drive the cancers.
Estradiol / E2 the more potent Estrogen may be necessary initially for some women if menopausal symptoms are too severe.
Otherwise I prefer Estriol / E3 based on the fact that it is already a liver Estrogen and doesn’t get converted into a “naughty” Estrogens and does much the same as Estradiol without the risk of initiating breast cancer.
Estriol / E3 is much like Progesterone quickly broken down and excreted and has a half-life of 5 – 10 hours.
See my article from my last blog related to the various concerns and risks – den kommer skal lige opdatere den
For women with their uterus intact the classic HRT using a combination of Estradiol with a Progestin for a period of 5 years is the preferred treatment.
Even though many studies show that taking this combination increases the risk for breast cancer
The uterine wall can always be activated by Estrogen, whether you are 40 years of age or 80 makes absolutely no difference. If there is enough Estrogen the wall will proliferate, form blood and become thick. Because a bleed doesn’t usually occur many women are not aware of the increased activity and long-term activation can increase the risk for uterine cancer.
For women without their uterus Estrogen can be used without a Progestin
All Progestins are not created equal
There are over 200 registered Progestin
Ever heard of the 4 generations of contraceptive pills?
Well this is describing the 4 generations of Progestins.
The goal with developing Progestins was to provide long-term protection of the uterine wall from the effects of Estradiol, thus decreasing the risk of uterine cancer. Something which bio-identical Progesterone couldn’t offer ‘then’
This was achieved, by altering the molecular structure but what wasn’t considered was could these changes have detrimental effects on other tissues?
Unfortunately, studies are showing quite clearly that combining Estradiol with a Progestin increases the risk for breast cancer even blood clots.
But a Progestin is not just a Progestin and some are less detrimental than others
How to get the pills
Oral hormones are only available through prescription.
For women who have had their uterus removed taking unopposed Estradiol or Estriol (without a Progestogen) is possible.
Women with their uterus intact must take Estrogens combined with a Progestogen.
Unfortunately, it is still common practise to use the non-bio-identical versions, even though micronized bio-identical Progesterone exists today in pill form under the names Prometrium and Utrogestan and studies state they offer optimal endometrial protection and can be used long-term.
Progesterone – good and bad for mood?
Progesterone supports the actions of GABA the neurotransmitter that brings calm in the nervous system.
When using micronized Progesterone in pill form you may feel more ‘relaxed, chilled aka sleepy’
Recent studies are demonstrating that some women have adverse reactions to their naturally produced Progesterone which can produce a paradoxical anxiety response. It’s called PreMenstrual Dysphoric Disorder (PMDD) or Neurosteroid Change Sensitivity and affects about one in twenty women.
If you suffer from PMDD using Progesterone as a supplement will increase anxiety.
Remember using certain types of Progestin together with Estradiol is clinically proven to increase the risk of breast cancer
Through the skin – transdermal
The transdermal route is relatively new and is most commonly available as patches, gels, creams or sprays applied directly to the skin, where the active bio-identical hormone will be absorbed locally and into circulation.
Patches are in general changed once or twice weekly, can fall off, may irritate and are not so attractive to look at.
My clinical experience is they seem less effective
Gels/creams/sprays are administered daily or every other day and may inadvertently be passed on to another person or pet if skin-to-skin contact occurs before the gel or cream has been fully absorbed.
An increasing number of studies are showing that the overall risk contra the benefit of transdermal HRT makes it a better/safer choice than the traditional oral HRT.
One reason might be that the hormones in the creams and patches are all bio-identical and another the liver is bypassed, the so-called first pass, which means the hormones gradually end in the liver for excretion and the dose of hormone much less.
But as this study states: ”Unfortunately, there are no large clinical trials comparing transdermal and oral therapies, and such trials will probably never be conducted.
Evidence to guide recommendations on the best route of hormone administration for individual women and prescribers will thus be limited to the ever growing volume of observational data.”
My observations, both personally and clinically are that transdermal hormone therapy is very effective and safer.
Many are under the misconception that transdermal Progesterone isn’t as effective as oral. This study demonstrates that this is not the case.
With that said combining Estradiol creams or gels with micronized Progesterone such as Utrogestan is also possible.
When using Estriol cream the question we should be asking, ‘is Progesterone protection necessary’?
The bioavailability of Estriol as a vaginal cream is up to 90% better than pill form.
Are not widely available today but have been used since the 1940’s
Small pellet-like implants made up of either Estradiol and / or Testosterone made in the US and UK by a licensed compounding pharmacist.
The pellets are inserted just under the skin usually in the tummy area and release Estradiol / Testosterone gradually over time and can last for several months before completely dissolving and thus being replaced.
As such they can be a convenient option, but the standardization is not optimal making it difficult to control the amount of hormone from one pellet to the next.
And as with any Estrogen if you still have your uterus, you’ll need to use a Progestogen as well, such as the Mirena coil or Utrogestan/Prometium pills
The Mirena coil releases a Progestin called Levonorgestrel into the uterus (and blood stream), which protects the uterine wall / endometrium from the effects of Estrogen. The medical world state that the coil only works locally, i.e. in the uterus but nevertheless some of the hormone is absorbed into the blood stream which can produce negative effects for some women, such as mood changes, bloating, bad skin, etc. If this occurs it is advisable to remove the coil
Levonorgestrel is a 2nd generation Progestin made from Progesterone as opposed to 3rd and 4th generations that are made from Cortisol or Testosterone, which seem to be involved with more negative effects. Being made from Progesterone may produce less side effects.
In South America an intrauterine device called a Progering, gradually releases Progesterone into the uterus and blood stream, but this not available in Europe.
Due to the Mirena hormone coil more women have preserved their uterus. Previously many women had their uterus removed during peri-menopausal times due to heavy bleeds, fibroids and flooding, which the Mirena coil fixes for most women. Is this good or bad, well neither or both, the result is that more women have a uterine wall that will need protecting if they use Estrogen replacement therapy
We are living in a new era
Women want to maintain their youthfulness, strength, passion and their figures, and have discovered that using Estrogen makes this possible and therefore would like to continue with ERT.
Can you continue with a hormone coil when you are 60 or 70 years of age, etc.?
Unfortunately, there are no studies and this question has not been of interest ‘until now’, so perhaps there will come some studies. But logically there is no reason why not.
But the other question that should be answered is do women need such large doses of Estrogen to maintain their youthfulness?
My opinion and personal experience is that, the answer is no.
How to go transdermal
Patches are prescription only
Creams, gels and spray with Estradiol are prescription only e.g. Estrogel, Evamist in most Europen countries.
Creams with Estriol can be bought in pharmacies without prescription in many countries, such as Ovestin.
Ovestin is sold as a vaginal cream but can also be used other areas such as wrinkles on the face and neck, etc.
Estriol cream can be bought on Biovea.com
When buying through the Internet make sure the product is USP standard.
What is USP Standard?
The United States Pharmacopeial Convention, Incorporated, (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed and consumed worldwide.
In many countries in Europe Progesterone creams can only be bought over the Internet.
USP standards are important, as is Progesterone has to be micronized to be absorbed.
So look for words USP and micronized when buying your Progesterone.
Also be aware that Wild Yams cream is not the same as Progesterone cream and may or may not be effective.
In Spain, Darstin Progesterone gel can be bought without prescription and Oestraclin an Estrdaiol gel can also be bought without a prescription
Implants and intrauterine devices, such as Mirena are prescription only and in Europe contain a Progestin usually Levonorgestrel.
In South America an intrauterine device called Progering containing Progesterone is available
The question everyone asks is how much should I use, how often and how long?
And the answer is – nobody really knows
If you are post-menopausal your ovarian production of Progesterone and Estrogen has ceased, but your Adrenals, fat cells, skin cells, brain, gut, etc. are still producing, just much smaller amounts and this production is very much affected by lifestyle choices.
Your natural production of hormones is monitored and regulated every millisecond to ensure your body is in balance and can function optimally.
If you are stressed your body’s natural production of Estrogen and Progesterone will be affected.
If your gut is out of balance body’s natural production of Estrogen and Progesterone will be affected.
If you are storing fat your body’s natural production of Estrogen and Progesterone will be affected.
Etc., etc., etc.
HRT supplies a specific amount of hormone with every dose regardless of your need.
Maybe one day you need more or maybe you need less.
So, the ability to be flexible and adjust the amount of hormone may be an advantage and transdermal creams, gels and spray offer this possibility.
As with any supplementation keep an eye on your life.
Ask yourself every morning
How do I feel?
How is life at the moment?
How did I sleep?
How is my diet?
In reality you are evaluating the level of stress in your life, the more stressed you are after menopause the more hormone you will likely need to supplement.
A starting point
How much Estrogen and how often?
You have no hormones
Start with the weakest hormone Estriol E3 at the lowest amount 1 cm or 1 pump once a day such as in and around your vagina and on your wrinkles
If it doesn’t help try twice a day
Remember to keep an eye on your uterine wall with annual ultra sound scans
Peri-menopause (the difficult years)
You have unstable hormones
Start with the advice for post-menopausal ladies
For some this may not be enough
Get a prescription for Estradiol cream, gel, spray and use as prescribed – but you must protect your uterine wall with some form of Progestogen
Progesterone (Utrogestan 200mg), maybe 10 days every 6 months doing this will create a bleed every 6 months or follow instructions from your doctor
A Progestin, best choice the Mirena coil and then there will be no bleeds
Difficult question to answer as again nobody knows.
The studies of the past with high doses of Estradiol and Progestins ended badly and HRT was put on the back burner for many years. So, there are no long-term studies to guide us.
I can only offer you my educated opinion based on experiences, both personal and through my many amazing clients.
Post-menopausal ladies using Estriol once or twice a day – I would say do it the rest of your life.
But remember there is, no science to support or reject my opinion.
Personally, I intend to maintain my female strength and vitality as long as I live.
JUST KEEP AN EYE ON YOUR UTERINE WALL
Peri-menopausal ladies use Estradiol and Progesterone / Progestin for the shortest time possible, which might be anything from 1 – 5 years.
Wean yourself off Estradiol and onto Estriol as quickly as possible.
A small amount of hormone can have an enormous effect
Using more hormone doesn’t give a bigger effect but will increase the risk for side-effects.
So, the advice I give my clients is “start low, you can always use more”, but if a small amount relieves your symptoms why take more?
Hope you enjoyed this article!
As always if I can help you more contact me on firstname.lastname@example.org
You can always find me at Club La Santa, Lanzarote www.clublasanta.com where I have my weekly workshops about male and female hormones.
Stay tuned for the next article