Understanding oestriol (E3)

TL;DR

Oestriol (E3), the weakest yet significant oestrogen, plays crucial roles during pregnancy and offers therapeutic benefits, including alleviating atrophic vaginitis and potentially managing multiple sclerosis symptoms. Despite its limited research, E3’s unique properties make it a valuable component in hormone therapy, especially in Europe where it’s widely approved and used. This article delves into E3’s production, benefits, and the ongoing debate surrounding its safety in bio-identical hormone replacement therapy.

Oestriol (E3) is the weakest of the three main oestrogens, with the other ‘main players’ being oestrone (E1) and oestradiol (E2).

E3 is only produced in the human body in any great quantities during pregnancy, being manufactured by the placenta. E3 is not secreted or produced by the ovaries, instead is the result of other processes that occur in the liver. E3 is available in both pill and vaginal cream or suppository form.

As a result of its perceived weakness, E3 has been somewhat left out of medical hormone research, despite having been shown to – unlike its oestrogenic friends – not fuel oestrogen-dependent cancers when used vaginally​1​.

This makes E3 a useful medical adjunct, for example in alleviating atrophic vaginitis while undergoing some forms of treatment for breast cancer, and for atrophic vaginitis/vaginal menopausal symptoms.

Oestriol (E3) cannot be metabolised into oestradiol (E2), unlike oestrone (E1). E3 on its own is weakly oestrogenic, but when E2 is present, E3 is anti-oestrogenic.

E3 has been found to inhibit the E2-induced proliferation of certain breast cancer cells via blockage of the GPER (G protein-coupled oestrogen receptor 1). E3 is approved in Europe, but not approved by the United States FDA or Health Canada for use as a therapeutic treatment in humans, however, it is used commonly in unregulated bio-identical hormone replacement therapy (BHRT) in North America.

BHRT E3 is available through compounding pharmacies over the counter, however, the debate still rages regarding its safety. Bio-identical hormones are still being researched.      

Levels of E3

Low levels of E3 are indicative of possible Down’s Syndrome and other foetal conditions. E3 has shown some use in managing multiple sclerosis (MS) symptoms, since being pregnant is known to suspend MS symptoms​2​ by what is understood to be a forced immune system shift. E3 levels in non-pregnant women are similar to the levels found in men.    

E3 levels during pregnancy

Oestriol levels rise markedly (1000-fold) during pregnancy, as it is synthesised by the placenta, with about 90 per cent of precursors to oestriol originating in the foetus. Circulating levels of E3 are kept in check by high excretion rates via the urine. 

Women who have been carried a pregnancy to term tend to have higher circulating E3 than women who have never been pregnant.

Foetal health is measured in some ways by measuring oestriol levels in the mother. If free oestriol is unusually low in a pregnant woman, it could indicate a chromosomal or congenital abnormality such as Down syndrome or Edward’s syndrome.

This is one test in the triple test and quadruple test for antenatal screening. These screenings are considered less definitive of foetal-placental health compared with the nonstress test. False positives can result when the foetus is in distress (preeclampsia, anaemia, impaired kidney function).      

Major brands of oestriol products

There are a few major brands of oestriol products across the world, with marketing for these products common in Europe. Some companies market oestriol succinate (Synapause), but none of these products have been approved by the North American FDA, but are sold regularly via compounding pharmacies over the counter as bioidentical hormone replacement ingredients. Topical creams containing E3 are unregulated in the US, but are available over the counter.

General list of brands of oestriol-containing products

  • Aacifemine
  • Blissel
  • Colpogyn
  • Elinol
  • Estriel
  • Estriol
  • Estriosalbe
  • Estrokad
  • Evalon
  • Gelistrol
  • Gydrelle
  • Gynasan
  • Gynest
  • Incurin (veterinary)
  • OeKolp
  • Oestro-Gynaedron
  • Orgestriol
  • Ortho-Gynest
  • Ovesterin
  • Ovestin
  • Ovestinon
  • Ovestrion
  • Pausanol
  • Physiogine
  • Sinapause
  • Synapause
  • Trophicreme
  • Vacidox
  • And others

References

  1. 1.
    Donders G, Neven P, Moegele M, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor®) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat. Published online April 10, 2014:371-379. doi:10.1007/s10549-014-2930-x
  2. 2.
    Sicotte NL, Liva SM, Klutch R, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol. Published online September 25, 2002:421-428. doi:10.1002/ana.10301


Jessica Lloyd - Vulvovaginal Specialist Naturopathic Practitioner, BHSc(N)

Jessica is a degree-qualified naturopath (BHSc) specialising in vulvovaginal health and disease, based in Melbourne, Australia.

Jessica is the owner and lead naturopath of My Vagina, and is a member of the:

  • International Society for the Study of Vulvovaginal Disease (ISSVD)
  • International Society for the Study of Women's Sexual Health (ISSWSH)
  • National Vulvodynia Association (NVA) Australia
  • New Zealand Vulvovaginal Society (ANZVS)
  • Australian Traditional Medicine Society (ATMS)
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