If a woman were lucky enough to live to middle age in the previous centuries, she really wouldn't want to try any of the then-available treatments for menopause. Prior to the 18th century, physicians thought that menstruation was a way to rid the body of toxins. To that end, menopause treatments meant attempting to restart the flow of blood, using leeches on genitals or other forms of bloodletting.

The symptoms of menopause were only recognized and named in the 1800s. By the early 1900s, crude experiments attempting to relieve the symptoms included transplantation of ovarian tissue into a uterine cavity and the sale of ovarian extracts or desiccated tissue for ingestion. Scientists were starting to understand that there was some important substance in the ovaries, but it took another 30 years to develop estrogen pills.

In 1941, the development of the first inexpensive hormone pill, called “premarin” (made from urine extracted from pregnant mares), set the stage for modern hormone therapy. But it has not been without its risks. In the 1970s, studies showed a link between estrogen therapy and increased risk for endometrial cancer.

After a drop in hormone use (and subsequent drop in endometrial-cancer cases) hormone therapy found a new popularity with addition of the hormone progesterone, which thins the lining of the endometrium and is thought to counteract estrogen's effect on endometrial cancer risk. Prescriptions for hormone therapy peaked in 1999 at 90 million.

Then came the results of the Women's Health Initiative, a multi-year study on long-term use of hormones to prevent chronic diseases such as cognitive decline or cardiovascular disease. One trial ended early in 2002 after it was found that the combination progesterone and estrogen therapy caused an increased risk for invasive breast cancer. The second trial, which examined the use of estrogen on its own, ended early in 2004 because it found an increased risk for stroke, despite the estrogen being linked to lower risk for coronary heart disease. The results offered a complicated intersection of risks and benefits that were difficult to interpret. For instance, while progesterone plus estrogen was found to increase risk for invasive breast cancer, it also lowered risk for endometrial cancer. Another complicating factor is that the risks changed as people aged. Only 10 percent of the participants in the WHI study were younger than 55. The younger the woman, the less risk involved in taking hormone therapy (depending on their personal history). Likely because of this confusion, the results were misinterpreted when applied to menopausal symptom management, says JoAnn Manson, a professor at Harvard Medical School and one of the principal investigators for the WHI.

The goal of the WHI trial was to assess the balance of benefits and risks when hormone therapy is used for chronic-disease prevention in postmenopausal women, says Manson. Researchers were studying if long-term use of hormones after menopause would help cut risks for cardiovascular disease, cognitive decline, hip fractures, different cancers, and diabetes. The trial did not evaluate use of hormones for hot flashes, which tend to occur in the early stages of menopause. For younger women (late 40s, early 50s) going through early stages of menopause and using hormones to treat hot flashes, the risks for stroke, blood clots, and cancer are lower compared to someone using hormones over decades as they age into their 60s and 70s.