During the 1930s, several independent research groups were exploring the effects of a substance now known as Progesterone. The first supplies were extracted from human placenta and consequently extremely expensive. The first semi-synthetic supplies were derived from steroid-like plant components at Parke Davis in 1940. From that point on, the drug companies have been in a race to improve on nature. They began looking for derivatives that would behave like progesterone but could be taken less frequently, or absorbed more efficiently, and—most importantly of all—be a brand-new molecule that would be eligible for patent protection.
By 1948, Dr. Katharina Dalton, a medical pioneer working in England, was already treating patients with different formulations of progesterone. She demonstrated success with injectable progesterone and, later on, with large doses delivered vaginally or rectally, providing relief even in some of the most severe cases of premenstrual syndrome (PMS).
It was not until the 1980s, when new technology of that era provided the ability to mill hormone powders into very tiny particle sizes that researchers began to challenge the belief that steroidal hormones were poorly absorbed when taken orally. In a breakthrough discovery, Joel T. Hargrove and Wayne S. Maxson found that this micronization process created more surface area, allowing for better absorption. They also found that progesterone was best absorbed when it was combined with edible oil.
Yet many practitioners were still skeptical. Generally speaking, most everything that survives stomach acid and is absorbed from the small intestine then passes through the liver for rapid breakdown. Little of the original substance makes it into the bloodstream. However, this is not how fats are absorbed. Rather than breaking down, fats are emulsified in the liver and then delivered via lipoprotein into the lymph system, and eventually into the bloodstream. In fact, Hargrove and Maxson documented very rapid absorption of oral progesterone in oil, peaking approximately two hours after ingestion.
The Beginning of Women’s International Pharmacy
In 1985, Wallace (Wally) Simons, RPh, founded Women’s International Pharmacy (WIP) with the goal of treating women with PMS using oral progesterone, based on the research being done by Hargrove and Maxson. According to Wally, there was so much controversy at the time that no one wanted to believe that PMS was a real problem, that progesterone had anything to do with it, or that oral doses of progesterone could be absorbed. Nonetheless, he jumped in—starting with one condition, one doctor, one preparation, and only one dosage strength—and thousands of women soon found relief.
In those early days, prescribed treatments consisted of large doses of oral progesterone, with an initial recommended dose of 100 mg taken four times daily. Some prescribers would recommend additional progesterone in the form of lozenges, suppositories or rectal solutions to provide further relief. In fact, some patient reports indicated that extremely severe symptoms, such as suicidal thoughts and tremendous headaches, were relieved very quickly with such high doses of progesterone. Patient reports also confirmed that progesterone could be absorbed from creams and gels on the skin and, in critical cases, via injection as Dr. Dalton first described.
Dr. Guy Abraham was also researching treatments for PMS in the 1980s, with a focus on the nutritional needs of women who suffered from PMS. He developed a vitamin and mineral supplement called Optivite, which contained a generous supply of vitamin B6, and which became a helpful adjunct to other PMS treatments. Not surprisingly, vitamin B6 is beneficial to the metabolism of progesterone.
A Fork in the Road
Fast forward to the late 1990s when Eli Lilly was about to lose the patent on their blockbuster drug Prozac , one of the first of a new class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs). In 1998, Lilly sponsored a meeting between FDA officials and Lilly representatives, in which they came to two pivotal conclusions:
- First, they agreed upon a new disorder that would be called Premenstrual Dysphoric Disorder (PMDD). Dysphoria is an emotional state marked by anxiety, depression, and restlessness, which meant that PMS was now considered a psychiatric disorder.
- Second, they agreed that it was appropriate to treat this new disorder with antidepressants.
In December of 1999, FDA advisors voted unanimously to not only validate PMDD as a new disease, but also approved Prozac as a treatment for it. Soon after, Prozac was remodeled and repackaged with lavender and pink colors, and given the name Sarafem. A massive advertising campaign ensued to make this new treatment appeal to “smart” women. The FDA also approved three other SSRIs for treatment of PMDD, which set the stage for long-term treatment of many women, during their child-bearing years, with SSRIs.
Around 2007 (less than ten years later), reports started appearing in medical journals linking long-term use of SSRIs with osteoporosis and bone fractures. While the cause or mechanism for this troubling association is still unclear, it certainly raises a red flag concerning the potential risks for long-term treatment with SSRIs. Perhaps it is time for progesterone to claim its position as the treatment of choice for PMS/PMDD symptoms.
Women’s International Pharmacy’s Continual Goal
Women’s International Pharmacy believes that each individual should be assessed by their practitioner for their unique needs. We have come a long way since the early 1990s when we recommended high doses of progesterone for treating PMS. We now know more about the relationships among progesterone and other hormones, particularly estrogens and thyroid. We also know that lifestyle choices, as well as interventions with food and nutrient support, can greatly influence PMS symptoms and treatment. We have better tools for assessing both physical and mental health conditions. When applicable, customized bioidentical hormone therapies can be a choice and progesterone is still an important option for PMS relief.