Progesterone Intolerance: What is it and how do we treat it?

Progesterone Intolerance: What is it and how do we treat it?

Progesterone is a special kind of hormone that comes from cholesterol and does a lot of important things in our bodies, especially when it comes to the menstrual cycle, pregnancy, making babies (embryogenesis), and breastfeeding. It's not just about having babies, though – progesterone also helps fight inflammation and keeps our immune system in check.

Let's talk about the menstrual cycle first. When a person with a uterus is getting ready to release an egg (ovulation), the level of progesterone goes up. It reaches its highest point around day 21 in a 28-day cycle, which is about a week before the period starts. This hormone is made by something called the ovarian corpus luteum, and it gets the uterus ready for a baby to stick there.

But if no baby sticks around, the corpus luteum shrinks, and progesterone levels drop. This drop is like a signal for the body to start the period.

Now, if there's a baby on the way, the progesterone levels keep going up. At first, the corpus luteum oversees making it, but later on, the placenta takes over. During pregnancy, progesterone helps the mom's body not fight against the baby growing inside, and it does other cool things like making sure the muscles in the uterus don't squeeze too much and stopping milk from coming out before the baby is born.

So, in simple words, progesterone is like the superhero hormone that helps with making babies and takes care of things during pregnancy. Cool, right?! But why does it matter in perimenopause and menopause?

Progesterone is used in many birth controls to suppress ovulation and in menopausal hormone therapy if you have an intact uterus to protect the uterine lining from growing and creating hyperplasia and cancer. Progesterone is often given in menopause therapy at bedtime because it helps with relaxation and has a sedative effect. It is relatively harmless and most tolerate it well.

How often do individuals not tolerate progesterone? It is a small percentage. I have seen 10-20% quoted, but I suspect this isn’t well reported and it isn’t something we talk about often in the US.

Progesterone intolerance refers to heightened sensitivity to the hormone progesterone or its synthetic form, progestogen. This condition can lead to symptoms reminiscent of premenstrual syndrome (PMS). In this information-packed blog post, we'll get into the symptoms, types of progesterone, associated risks, and potential management strategies for those grappling with progesterone intolerance.


Symptoms of Progesterone Intolerance

Progesterone intolerance manifests in three main areas: psychological, physical, and metabolic. Psychological effects may include anxiety, irritability, and mood swings, while physical consequences range from acne to breast tenderness. Metabolic reactions can impact cholesterol, blood pressure, and blood sugar levels.

Common symptoms of intolerance – bloating, headaches, cramping, irritability or anger, depression or anxiety, breast pain, fatigue or acne.


Understanding the two main types of progesterone

Progestogens (general category that includes synthetic progestins and progesterone) commonly coadministered with estrogen in women with a uterus include meddroxyprogestedrone acetate (MAP), norethindrone acetate (NETA), and micronized progesterone (MP).

Medroxyprogesterone acetate (Provera), levonorgestrel, and NETA are synthetic progestins.

MP is structurally identical to the progesterone produced by the corpus luteum (body identical/bioidentical). MP is also known as micronized progesterone or Prometrium. Typical dosing 100-200mg.


Progesterone in Hormone Replacement Therapy (HRT)

For women on HRT, progesterone is essential to counteract the effects of estrogen, particularly for those with a uterus. The choice between cyclical or continuous progesterone regimens depends on factors like recent periods. Unfortunately, intolerance symptoms often prompt women to discontinue HRT.


What options do we have to manage Progesterone Intolerance?

  1. Systemic Progesterone: Opt for body-identical progesterone, such as micronized progesterone (Provera), which is less likely to trigger negative reactions. Adjustments in dose, administration, or duration may be explored with your doctor.
  2. Local Progesterone: Administer progesterone vaginally through tablets, reducing systemic side effects. The Levonorgestrel IUD (Mirena), releasing progestogen directly into the uterus, again reducing systemic side effects.
  3. Alternative hormone therapy options: Duavee is an estrogen therapy for postmenopausal women with a uterus that uses bazedoxifene in place of a progestin. Congugated estrogens provide significant relief from moderate to severe hot flashes due to menopause and prevent postmenopausal bone loss. Bazedoxifene is an estrogen agonist/antagonist, also known as a selective estrogen receptor modulator or SERM, which helps protect the uterine lining from the thickening and leading to cancer.
  4. Surgical Intervention: In severe cases, when other options fail, a hysterectomy may be considered. This is a serious decision requiring thorough discussion with a gynecologist.


Progesterone Intolerance: A Personal Journey

Women's experiences with progesterone vary widely. Some thrive on its benefits, while others battle side effects like bloating, mood changes, or water retention. This diversity underscores the importance of personalized management plans, from adjusting dosage to exploring alternative hormone therapy formulations.



Understanding progesterone intolerance empowers women to navigate their hormonal journey effectively. From identifying symptoms to exploring tailored management options, this guide aims to provide valuable insights into progesterone-related challenges and potential solutions.


Seeking Help

If you're struggling with progesterone intolerance and its impact on contraception or HRT, consult your healthcare professional. Specialized advice from a menopause specialist can offer in-depth discussions on progesterone intolerance and personalized treatment options.

Remember, your hormonal journey is unique, and finding the right balance requires collaboration with healthcare providers who understand your specific needs.


Disclaimer: The information provided is for educational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional for personalized guidance on your health and hormonal management.