Help! There is an Estrogen Shortage!

Why this is happening and tips for navigating the shortage

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I’ve received comments here from several people in Canada, where they are currently experiencing estrogen shortages, and who can’t find pharmacies to fill their prescription for an estradiol patch. What should they do?

This isn’t a Canada-only issue. There have been estrogen shortages in many parts of the world on and off for several years. This isn’t an estrogen-only issue, either. Many drugs have been in short supply for the past several years. Between 2021 and 2022, the number of drug shortages jumped 30%. In the United States, when we experience a drug shortage, it’s typically in short supply for about 1.5 years, but the average duration of shortages is longer for some classes of drugs. For example, for chemotherapy drugs, it’s 878 days; for hormones, it’s 1,201 days. More than fifteen drugs essential for critical care have been in short supply here for over a decade. This is a major health issue.

Most of the difficulty with accessing medications, including estradiol, is supply chain-related. People need to know that pharmaceutical supply chains are often more precarious than you might think, and these underlying issues were only exacerbated by the pressures of the COVID-19 pandemic and the US-China trade war. 

The drug supply chain over relies on foreign manufacturers that are often in one part of the world for raw materials and/or the medications themselves. According to a report from the U.S. government, “90 to 95 percent of generic sterile injectable drugs for critical acute care in the U.S. rely on key starting materials and drug substances from China and India.” And there may only be a few processing plants that can convert the raw material into the final pharmaceutical. This is a case of having all the eggs in one basket, but several times for each medication. One factory-related issue and overnight 50% or more of the supply of one medication could easily be affected. 

Here’s an example. Right now, I can’t get Brexafemme, an antifungal medication, for my patients with resistant yeast infections because there was a factory-related issue leading to potential contamination of the drug with another medication. Production had to be stopped. I don’t know how much of the company’s drug stock was affected. I’m guessing all of it, or they had very little stocked as the supply dried up immediately. Although, it’s always possible another healthcare system scooped up the remaining drug. Everything is so opaque, so all I (and my suffering patients) can do is wait for the company to sort the issue out, get production back online, and hope their projected timeline is accurate. It’s a brand-name medication, so no one else makes it.

The devastation of Hurricane Maria triggered a major drug crisis in 2017, as a lot of U.S. medications are made in Puerto Rico. The New York Times reported that thirteen drugs made by a single manufacturer were in short or critical supply because of the hurricane. This means when one manufacturer loses all their manufacturing capabilities because of a natural disaster, there may not be another company to pick up the slack. Most manufacturing is highly specialized, so it’s not possible, for example, to all of a sudden start making estradiol at a plant that makes penicillin, in the same way that a factory that makes shoes can’t all of a sudden start making socks. 

For a drug like estradiol, it’s not just about having the manufacturing facilities and the workers. It’s also about the soybeans that are grown to produce the chemical that is ultimately converted into estradiol. If there is a crop failure, which is becoming more of an issue with climate change, that also affects production, and recovery can take an entire growing season or possibly longer. If there are only a few suppliers of soybeans or parts of the world where the soybeans are grown, the risk of a crop failure in the supply chain is even higher. 

When there is a shortage, generic medications are often the hardest hit, and many people rely on generics for menopause hormone therapy. This is because generics are made in response to direct customer product orders. Governments are involved here, predicting how much of a supply of drug A or B they will need. Consequently, there aren’t warehouses of pre-existing generic drugs available to fill the gap when there is a supply chain issue. This also means that shortages can be the result of poor order forecasting by agencies that didn’t anticipate the need. Generics also have narrower profit margins, so there is often more outsourcing of different aspects of manufacturing to save money, including shorter-term contracts, which may be more fragile. Basically, there are way more eggs in one basket with generics.

The unfortunate reality is there have been lots of shortages of critical medications, and estradiol is sadly just one more on a long list. And government agencies need to address this because it’s a major health concern.

Now that you know the background, let’s tackle what to do if you can’t get your estradiol. 

Talk With Your Pharmacist

Sometimes shortages are weirdly regional, and your pharmacist may be able to locate a supply. I’m told many pharmacists are a part of massive WhatsApp groups that help find medications in times of need.  

Switch from a Generic to a Brand Name or Vice Versa if that Possibility Exists

Brand names may be less affected by supply chain issues, although admittedly, this isn’t always the case. One downside is brand names may also be more expensive. 

Consider a Different Dose of Patch and Adjust Accordingly

Cutting a patch to get one that works for you dose-wise is an option. This means that if you can get a 75 mcg estradiol patch, you can cut it in half to get a 37.5 mcg equivalent or a 50 mcg patch to get a 25 mcg patch. For someone who uses a 50 mcg patch, one of the more common doses, I would advise half of a 75 mcg patch, meaning 37.5 mcg, as that is very likely to work well and would be better than going without. 

Not all patches can be cut, though. Patches are either matrix, meaning the medication is in the adhesive, or reservoir, meaning a liquid with a rate-limiting membrane. Cutting a reservoir patch to get two small patches with lower doses doesn’t work because the medication will seep out, rendering the patch useless or next to useless. A matrix patch can theoretically be cut in half, although companies rarely have this data available. They don’t want you cutting a patch; they want you to buy a new one in the new strength. 

One study shows that matrix estradiol patches can be cut as long as the second half is used within a month, and I definitely tell my patients they can cut their matrix patches. A circular patch should just be cut in half. This diagram is from the BC Children’s Hospital with instructions on how to cut a rectangular patch in half or even in quarters. 

I believe Estraderm is the only reservoir patch, so if you have a different patch, cutting is an option, but you should always double-check that your patch is matrix (okay to cut) on the product monograph. Here is a screenshot from the Estraderm product monograph, which describes the “rate-limiting membrane,” telling you this is not okay to cut. 

And here is the same information from a Climara patch, which describes an “adhesive matrix,” so it's okay to cut. 

Switch to a Different Topical Estrogen

If estrogen patches aren’t available, one of the other topicals may be. Here is the conversion chart that I have been promising. I sourced this from several reputable pharmacy sites, looked at the average estradiol levels in package inserts, and also used the few studies that exist. Understand that these products are rarely studied head to head, so some of this is “best guess.” Consider these as launching points for a conversion.

(And yes, I know that the conversions from transdermal to oral are different in the UK, and I have no explanation for that, but the patch to oral conversion is not my best guess; it’s in every US and Canadian guideline). 

Switch to an Oral Estrogen

While we believe transdermal has the lowest risk of clots, oral estradiol and Premarin are fine options for people at low risk for cardiovascular disease. Oral estrogen isn’t an option for someone with an ASCVD score greater than 5% (read more here) and someone who is at high risk of clotting. I’d also be concerned about switching someone who is age 65 or older to oral therapy (cardiac risks and risks of clots rise with age). The decision to convert to an oral estrogen should be made in consultation with your own provider, but remember, if you were starting hormones at age 50 and didn’t want a topical or you wanted Duavee (read more here) and were low risk, we’d prescribe an oral estrogen. Also, I sometimes switch people who aren’t getting the benefit they need from a transdermal to an oral estrogen, as the metabolism is different, and that may be better for some people.

Take a Higher Dose of Prometrium

Oral micronized progesterone in doses of 300 mg daily can help quite well with hot flashes. This is also something to consider for people who can’t take oral estrogen because of cardiac or clotting risks. Again, this should only happen in consultation with your doctor. 

See How You Do With a Non-Hormonal Medication for Hot Flashes

Options are:

• Fezolinetant, which is the new medication (read more here)

• Selective serotonin reuptake inhibitors, such as paroxetine

• Serotonin-norepinephrine reuptake inhibitors, such as venlafaxine

• Gabapentin (I have a lot of success with gabapentin)

• Oxybutynin (probably the least effective of the choices here)

Consider Seeing How You Do Off Estrogen

If you are someone who has been on estrogen for a while, say six or seven years, it’s possible the symptoms that prompted you to start hormones have now stopped or have improved significantly. So, stopping therapy might also be possible for some people.

Summary

Hopefully, some of you find some of these suggestions helpful. 

On a bigger note, we should all be concerned about the drug supply chain. And so, if you have the bandwidth, this is something to discuss with your elected representative because, left as it is, the drug supply chain is likely to become more precarious. 

And if people need a similar post for vaginal estrogens, let me know in the comments!

As always, the information here is not direct medical advice.

References

Ankarberg-Lindgren C, et al. Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures. Endocr Connect. 2019;8(4):360

Martin KA, Barbieri RL. Preparations for menopausal hormone therapy. UpToDate. 2023.

Santoro N, Allshouse A, Neal-Perry G, et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study. Menopause 2017;24:238-246.

Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8(Suppl 1):3-63.

Endocrinology Advisor, Oral and Transdermal Estrogen Dose Equivalents https://www.endocrinologyadvisor.com/clinical-charts/oral-and-transdermal-estrogen-dose-equivalents/

Converting Between Estrogen Products. The Pharmacists’ Letter/the Prescriber’s Letter. 2009:25, Number 251109.

The United States Senate Committee on Homeland Security and Governmental Affairs. Short Supply, the Health and National Security Risks of Drug Shortages.