Mare’s urine and women’s health go back in time together

Clinical
By
Dr Leigh Dayton
-

It seems an unlikely pairing: older women and pregnant horses. But there is a connection: urine. The golden fluid they both produce contains conjugated oestrogen, the sex hormone that regulates female reproduction.1

In ancient times, symptoms of menopause, from infertility to ‘female weakness’, were widely viewed as the result of ‘bad blood’ no longer being removed by menstruation. Hence, as clinical consultant Jura Lasas notes, periodic bloodletting emerged ‘to help restore balance and soothe symptoms’.2

But in the late 1700s, physicians changed direction. Symptoms occurred, they concluded, because ovaries dried up or the uterus shrank, ending menstruation, a condition French physician Charles de Gardanne dubbed ‘ménopause’ in 1828.2

So could menopause be halted by replacing these organs? By the 1890s, companies like Merck were saying yes.2

They did so by producing pills containing ground cow ovaries, unbeknown to them a source of symptom-regulating oestrogen. While the term ‘hormone’ was not coined until 1905 by University College London physiologist Ernest Henry Starling, they were laying the groundwork for effective menopausal hormone therapies (MHTs) powered by mare’s urine.2,3

Why mare’s urine?

Along with water, urea and numerous organic and inorganic substances, pregnant mare’s urine contains high concentrations of conjugated equine oestrogen. Oestrone sulfate and oequilin sulfate are the most common of these oestrogens.4,5,6

This is significant because the oestrogens control functions of the female reproductive system in humans and horses alike. They do so by binding to specific receptors which, in turn, activate biochemical events that control gene expression.7

But oestrogen declines as women age. It falls from a peak of 400 picograms per millilitre (pg/mL) to a trough as low as 2 pg/mL. The trough is menopause.1

Common menopause symptoms include vaginal dryness and hot flushes, as well as mood swings, brain fog and osteoporosis.1,2,8

Modern moves

From 1928, mare’s urine featured prominently in research leading to the development of conjugated estrogens (Premarin), a top-selling MHT to this day. By then scientists knew that menopause was caused by decreasing levels of oestrogen.2

Leading biochemists James Collip of Canada’s Ayerst Laboratories and Germany’s Adolf Butenandt with Schering AG were racing to develop MHT products. While both scientists eventually used mare’s urine to develop their products, they began working with extracts collected from Canadian women in late-pregnancy.9

Butenandt and Schering were first to market. Conjugated estriol (Progynon) was launched in 1928. Collip followed with conjugated estriol (Emmenin), a highly similar product released by Ayerst in 1930 in Canada and 1934 in the US.9–11

However, both companies questioned the commercial viability of human material, so they switched to pregnant mare’s urine.9

‘Apparently the hormones extracted from horse urine didn’t have the same taste and odour issues as those derived from human urine,’ notes Mayo Clinic’s Thom Rooke.11

The Canadian team won the MHT race by developing Premarin (PREgnant MARes’ urINe). It was first marketed in Canada in 1941 and the US the following year.4,12

Since then, Premarin has gone global. Despite some ups and downs, it is predicted to be worth US$2.5 billion by 2033. The mares will be busy.13

References

  1. Cleveland Clinic. Estrogen. 2026. At: https://my.clevelandclinic.org/health/body/22353-estrogen
  2. Lasas J. The history of menopause: a story told through time. Ticking Biology. 18 Jun 2025. At: https://tickingbiology.com/history-of-menopause/
  3. Lasas J. How mares transformed medicine: the history of hormone replacement therapy (HRT). Ticking Biology. 13 Jun 2025. At: https://tickingbiology.com/history-hormone-replacement-therapy/
  4. North American Equine Ranching Information Council. Care and oversight of horses managed for the collection of pregnant mares’ urine (PMU). NAERIC. 2014. At: https://naeric.org/assets/pdf/PMU-WhitePaper.pdf
  5. Wortley Axe J. The horse: its treatment in health and disease. Glasgow: Gresham Publishing Company. 1906.
  6. Scanes CG. Animal attributes exploited by humans (nonfood uses of animals). In: Scanes CG, Toukhsati S, eds. Animals and human society. San Diego: Academic Press. 2018. pp. 23–56.
  7. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol 2019;116:135–70.
  8. Cleveland Clinic. Menopause. 2026. At: https://my.clevelandclinic.org/health/diseases/21841-menopause
  9. Seaman B. The greatest experiment ever performed on women: exploding the estrogen myth. New York: Seven Stories Press. 2003.
  10. Science Museum Group. Glass bottle for ‘Progynon’ pills, United Kingdom, 1928–1948. Object A629954. Science Museum Group Collection Online. At: https://collection.sciencemuseumgroup.org.uk/objects/co185655
  11. Rooke T. The quest for cortisone. East Lansing: Michigan State University Press. 2012.
  12. North American Equine Ranching Information Council. History of Premarin. NAERIC. 2026. At: https://www.naeric.org/about.asp?strNav=11
  13. Strategic Revenue Insights. Premarin-API market size, future growth and forecast 2033. 2026. At: www.strategicrevenueinsights.com/industry/premarin-api-market