Progesterone Hypersensitivity: How Pregnancy Can Make You Allergic to Your Own Hormones

Expert: Dr. Kim Langdon Cull

After giving birth to my only child in the fall of 2015, it took forever for my menstrual cycle to return. With my history of endometriosis, I wasn’t exactly looking forward to it, and enjoyed a reprieve until my son was fully weaned at 18 months. I was expecting a return to painful periods, but I had no idea what my body had in store.

I developed severe tree nut and peanut allergies in my late twenties but have generally been excellent at avoiding them. So imagine my surprise when I had an allergic reaction  out of the  blue to the soynut butter I always consumed as a substitute to the usual PB&J! Thinking I had developed a soy allergy, I cut out soy. But next, it was orange juice, then asparagus, followed by blueberries, and finally, coffee. I met with my allergist who tested me for these and other foods only to find that I’d tested negative to everything. The daily food and activity log she had me keep showed no similarities in food families or other patterns, such as reactions after combining a food with exercise or NSAIDS. 

I was at a loss until I pulled out the many bills from my frequent ER trips, often by ambulance. Looking at the dates on them, I noticed that the reactions were occurring monthly, often within a few days of each other. I had long logged my cycle in a journal due to endometriosis and overlaid the dates of anaphylaxis with the dates of my cycle. A pattern finally emerged! All the events were within 7-10 days of my period starting. I called my doctor and made an appointment. 

Most people familiar with pregnancy are aware that the pregnant person’s progesterone levels increase slowly during the first trimester and then more rapidly in the second and third trimesters, as this hormone works to thicken the uterine lining, suppress contractions, and transform the shape and structure of the uterus. 

However, in some people, this high amount of progesterone actually sensitizes their bodies to the hormone, resulting in progesterone hypersensitivity.

What Is Progesterone Hypersensitivity?

Progesterone hypersensitivity is a condition in which the body develops an IgE-mediated allergy or autoimmune response to endogenous progesterone (produced by the body), exogenous progestins (external, such as through medications), or to both forms of the hormone. Affected persons can be highly allergic to even small amounts of these hormones or may only react to “spikes” in progesterone or progestins, such as those occurring in the luteal phase of the menstrual cycle or when the person is given progestins for fertility treatment, endometriosis, or other medical circumstances.

Causes and Risk Factors for Progesterone Hypersensitivity

Progesterone hypersensitivity can impact people of reproductive age from their first period to menopause, though menstruating adults in their late 20s are most at risk. 

Pregnancy and/or exposure to exogenous progestins (oral contraceptives, fertility treatments, certain IUDs, contraceptive vaginal rings, certain supplements or medications) increase the risk of developing progesterone hypersensitivity. 

Signs and Symptoms of Progesterone Hypersensitivity

Symptoms are generally cyclic and arise or worsen during the luteal phase of the menstrual cycle or after exposure to exogenous progestins.

• Skin symptoms (rashes, hives, blisters, itchiness, eczema, inflammation, and swelling)
• Respiratory symptoms (wheezing, increase in asthma symptoms)
• Systemic or severe symptoms (anaphylaxis or other severe symptoms that affect two or more body systems)

Challenges in Diagnosing Progesterone Hypersensitivity

Diagnosing progesterone hypersensitivity can be difficult for several reasons. Progesterone hypersensitivity is considered a rare allergy, with only 200 cases reported in the medical literature. However, it may be underreported and there are no official rates of incidence. A private Facebook group called “Autoimmune Progesterone Dermatitis,” which is another name for the condition, has 3.3K members and is active daily, suggesting that self-diagnosis is leading a significant number of patients to consider progesterone hypersensitivity as a possible match for their symptoms. 

Because progesterone hypersensitivity is considered rare, many obstetricians and gynecologists are unfamiliar with the condition, and even some allergists are under trained in recognizing its manifestations. Additionally, skin tests for progesterone have low sensitivity in detecting the condition, which may cause providers to rule it out as a possibility and not suggest further testing. Just a few years ago, Dr. Jonathan Bernstein developed a progesterone-specific ELISA assay to diagnose progesterone hypersensitivity and his lab will test mailed-in specimens, which can be a helpful tool for medical providers outside of the Cincinnati area where he practices. 

More common diagnoses also must be ruled out, such as chronic or spontaneous hives or allergies to NSAIDS or foods. Further, conditions such as catamenial anaphylaxis and estrogen hypersensitivity are also responses to hormones and the menstrual cycle and will need to be considered as possible diagnoses by one’s care team.

Managing Progesterone Hypersensitivity

The treatment options for progesterone hypersensitivity are largely based on symptom severity and whether the patient wishes to become pregnant or has completed childbearing. For those wishing to expand their families, desensitization to progesterone may be possible in some cases, which may allow for safer fertility treatments and pregnancy. 

Use of anti-allergy medication, such as second-generation H1 blockers like Zyrtec and Claritin can also be used for more mild symptoms along with topical creams to treat dermatitis. 

For people who are done childbearing, more treatment options are available. Constant daily oral contraceptives, in which the patient does not take the placebo pills, can halt the menstrual cycle and provide relief. While it may be counterintuitive to prescribe progestin-only or combined oral contraceptive medications, since both include forms of progesterone, for patients who tolerate small doses of the hormone, these are easy and affordable methods to avoid the spikes in progesterone that trigger symptoms. 

Omalizumab (Xolair) can also be used to reduce the overall circulating IgE and thus reduce symptoms. GnRH Agonists can also be used to prevent ovulation. Danazol and Tamoxifen can also be used, though they are not often first-line treatments due to side effects. 

In cases refractory to other treatment options, a bilateral salpingo oophorectomy may be necessary.

What to Do If You Think You Have Progesterone Hypersensitivity

• Make an appointment with an allergist or immunologist and inform your obstetrician, gynecologist, or fertility specialist of your concerns. 
• Keep track of when your symptoms occur in relation to your cycle. Dr. Renita White suggests, “One of the best things you can do is keep a menstrual calendar or diary to document the timing of your symptoms in association with your cycle. Each time you experience rash, itching, or another symptom, note when it happens, detailing the length, what exactly happens, what helps the symptoms, and what worsens them. Reviewing this information with your provider can help to identify any patterns that are consistent with progesterone hypersensitivity.”
• In addition to the above details, note what you’re doing when symptoms flare (exercise, recent foods, other medications or supplements, sun exposure, etc.). This step can help rule out other potential triggers.
• Avoid consuming foods or supplements that are known to impact hormone levels unless under the direction of a physician.

What to Do Once You Have a Diagnosis

• Take all medications as prescribed and make sure not to skip doses, especially more for more than 3 days in a row.
• Talk to your doctor if your family planning situation or choice changes.
• Make sure to check with your physician or pharmacist before taking any additional medications or supplements that might impact the effectiveness of your current medication regime. For example, evening primrose oil, Plan B, and other over-the-counter products may impact your treatment plan. 
• Find support! The sometimes-devastating and often-confusing impacts of a progesterone hypersensitivity diagnosis can be hard to navigate on your own. Because the condition is fairly rare, it may be difficult to locate support in-person, especially if you live in a more rural area. However, there are online support groups, such as the Autoimmune Progesterone Dermatitis Facebook group mentioned earlier, as well as other online forums where you can ask questions, gain insights, and find folks who are also dealing with this disease. 
• Be prepared to explain your diagnosis to medical providers, family, and perhaps even strangers. One of the difficulties of having a rare condition is that people are simply not aware that being allergic to hormones is even a possibility and may not understand the implications of this diagnosis, even if they work in the medical field. 
• If you suffer from severe symptoms or anaphylaxis, consider getting a medical alert bracelet or necklace. 

While progesterone hypersensitivity may be rare and tricky to diagnose, there are ample treatment options for this condition and most patients find a plan that works for them, even if it’s not the first treatment they try.