Polymer Chemistry: Patching Up Holes in Menopause Therapeutics

Hot flashes, night sweats, insomnia, and anxiety are just a few of the taxing symptoms that come with menopause. These symptoms occur because the ovaries begin producing less estrogen during menopause, which has wide-reaching implications for the entire body. Pharmaceutical scientists at Xinjiang Medical University have developed a compound estrogen-progesterone patch that offers a promising new avenue for managing these symptoms.

Transdermal estrogen patches are a common therapeutic used to alleviate menopause symptoms. They are adhesive patches, often worn on the lower back, and they contain estradiol, the most abundant form of the steroid hormone estrogen.

The estradiol is slowly released from the patch over several days and absorbed into the body through the skin. It reduces the severity of short-term menopausal symptoms, such as hot flashes, and also plays a role in preventing long-term symptoms, such as osteoporosis and the thinning of vaginal tissue.

A major limitation of these patches is that the administration of estradiol by itself can put patients at an increased risk of developing cancer. To reduce this risk, supplements of progesterone, another steroid hormone produced by the ovaries, need to be taken while using estradiol patches. 

Supplemental progesterone is often taken orally or vaginally. In a paper published in the European Journal of Pharmaceutical Sciences, Dr. Mei Wang and collaborators designed an estradiol patch that also releases progesterone, eliminating the need for additional progesterone supplements.

Chemical structures of estrogen and progesterone. By Ada Fiala.

There are already some compound estradiol-progesterone patches on the market, but they all contain progestins, synthetic forms of progesterone with chemical structures that are similar, but not identical to, natural progesterone. There is some evidence that bioidentical progesterone may be associated with reduced side effects and better health outcomes in the long term compared to progestins. Wang’s study uses progesterone that is identical to the progesterone naturally produced by the ovaries. 

The compound estradiol-progesterone patch created by Wang and collaborators required careful formulation. First, the estradiol and progesterone are connected into long chains called polymers. The polymers form cross-linked networks with each other and create a film.

The polymers in the film will slowly degrade over time, releasing the drugs from the patch and allowing them to penetrate the skin and permeate into the tissues underneath it. To create a wearable patch, other types of molecules were added to the film in addition to the drugs. 

The patch contains molecules called plasticizers, which make it more durable and flexible by changing how the estradiol-progesterone polymers interact with each other. The patch also contains permeation enhancers, which are molecules that interact with the patient’s skin to make it easier for the released progesterone and estradiol to pass through it. On top of it all, other types of polymers need to be added to the film to make it adhesive. Crucially, none of these additional components can interfere with the release of the estradiol and progesterone. 

The paper screened several combinations of plasticizers, permeation enhancers, and adhesives to find the optimum combination.

Researchers then simulated menopause in the mice by removing their ovaries and studied the effects of their optimized patch on the mice’s hormone levels. Overall, they found their patch to effectively raise the levels of estradiol and progesterone in the mice’s blood to pre-menopausal levels and to reduce uterine atrophy and vaginal wall thinning over a two-week period. 

Comparing mice treated with their patch to mice treated with an estradiol-only patch and a supplemental progesterone injection, they found the concentrations of progesterone in the mice’s blood to remain more stable in the group treated with their patch. This suggests that the simultaneous delivery of estradiol and progesterone from a transdermal patch may lead to more stable hormone levels than the delivery of progesterone through oral or injectable supplements.

While further testing needs to be done on the health outcomes of long-term use of the patch, Dr. Wang’s group’s combined estradiol and progesterone patch is a promising step towards simplified management of menopause symptoms.

By Ada Fiala