Premarin is made from the urine of pregnant horses. The name itself is a shorthand for “pregnant mares’ urine.” First approved by the FDA in 1942, it remains one of the most widely prescribed estrogen medications in the United States, now manufactured by Pfizer.
What’s Actually in the Urine
Pregnant mares produce urine that is rich in naturally occurring estrogens. Premarin contains a mixture of these estrogens, collected and processed into a pharmaceutical product. The two primary compounds are sodium estrone sulfate and sodium equilin sulfate. It also contains several secondary estrogens, including forms of dihydroequilin and estradiol.
Altogether, Premarin contains at least 10 different estrogenic compounds. Some of these, like equilin, are unique to horses and are not found naturally in the human body. This is one of the key distinctions between Premarin and other estrogen therapies: it delivers a complex cocktail of horse-derived estrogens rather than a single human-identical hormone.
How Horse Estrogens Differ From Human Estrogens
The estrogens in Premarin are structurally different from the estrogen your body produces (called estradiol, or 17β-E2). These structural differences change how the hormones interact with estrogen receptors in your cells. Human tissue has two types of estrogen receptors, and horse-derived estrogens activate them differently than human estradiol does. They also behave differently depending on the tissue type, meaning they can have varying effects in the breast, uterus, brain, and bones.
Research has found that horse estrogens are generally less potent on one of the two receptor types compared to human estradiol. This reduced potency comes from differences in molecular flexibility and how the compounds physically fit into the receptor. The clinical significance of this is still debated, but it’s the reason some patients and physicians prefer bioidentical estrogen products that use estradiol matching what the human body naturally makes.
How the Urine Is Collected
Premarin’s raw ingredient comes from specialized ranches, primarily in Canada, where pregnant mares are fitted with urine collection devices during the later months of their pregnancies. The mares are typically kept in stalls during the collection period, which runs roughly six months of the year during gestation. Outside of collection season, the horses live on pasture.
The industry has drawn scrutiny from animal welfare organizations over the years. The American Association of Equine Practitioners reviewed the practice and concluded in 2010 that urine collection, when conducted according to the recommended Code of Practice, “represents responsible management of horses” and “should not result in abuse, neglect or inhumane treatment.” Independent veterinarians conduct herd health reviews of equine ranches, and a dedicated research facility in Canada oversees welfare standards for horses in the industry. Pfizer maintains that its use of horses is justified as long as herd management meets or exceeds veterinary criteria.
Critics counter that confining horses for months and the fate of the foals born each year remain ethical concerns regardless of industry oversight. This controversy is a significant reason many patients seek alternatives.
What Premarin Is Prescribed For
The FDA approves Premarin for several uses. The most common are treating moderate to severe hot flashes and night sweats during menopause, and relieving vaginal dryness and discomfort caused by declining estrogen levels. It is also approved for preventing postmenopausal osteoporosis and for treating certain hormone-related conditions, including low estrogen from ovarian failure.
Premarin comes in oral tablet form and as a vaginal cream. The cream contains 0.625 mg of conjugated estrogens per gram and is used for localized symptoms.
The medication carries a boxed warning, the FDA’s most serious safety label. Estrogen-alone therapy is associated with increased risks of endometrial cancer in women who still have a uterus, as well as elevated risks of stroke and deep vein thrombosis. The Women’s Health Initiative, a large clinical trial, also found an increased risk of probable dementia in women 65 and older who used conjugated estrogens alone over about five years. When combined with a progestin, the risks expand to include heart attack, pulmonary embolism, and invasive breast cancer.
Alternatives That Don’t Come From Horses
If the source of Premarin is a concern, several alternatives exist. Bioidentical estradiol, which is chemically identical to the estrogen your body produces, is available in pills, patches, gels, sprays, and vaginal rings. These are typically synthesized from plant sources like yams or soy.
There are also synthetic conjugated estrogen products designed to mimic Premarin’s mixture without using animal-derived ingredients. These plant-based alternatives contain lab-created versions of the same types of estrogen compounds found in mare urine. Your prescriber can help determine which formulation fits your needs, since the clinical effects of these different estrogen types are not always interchangeable.