Progesterone Intolerance

Progesterone intolerance , affecting approximately 10–20% of women, occurs when individuals are particularly sensitive to progesterone or its synthetic counterpart, progestogen. While progesterone typically has calming, anti-anxiety properties, some women experience adverse reactions, leading to symptoms similar to premenstrual syndrome (PMS).


Symptoms of Progesterone Intolerance:

Psychological : Anxiety, irritability, aggression, restlessness, panic attacks, low mood, poor concentration, forgetfulness, and heightened emotions.

Physical : Acne, greasy skin, abdominal cramping or bloating, fluid retention, fatigue, headaches, dizziness, and breast tenderness.

Metabolic : Negative effects on cholesterol, blood pressure, and blood sugar regulation. Notably, natural (body-identical) progesterone does not usually have these metabolic effects.


Types of Progestogens

Natural (Body-Identical) Progesterone : Structurally identical to the hormone produced by the ovaries, brain, and other organs, and derived from sources like yam root or soy. It is associated with fewer side effects and lower risks compared to synthetic versions.

Synthetic Progestins:  Chemically created and structurally different from natural progesterone they were created to stop endometrial thickening.   These are commonly used in various contraceptives and some HRT formulations. Intolerance symptoms are more prevalent with synthetic progestogens, which are also linked to a slightly increased risk of blood clots, heart disease, and breast cancer.


Who Is Affected?

Women who experience premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) are often more at risk of progesterone intolerance.  

Progesterone intolerance can also be experienced by those using contraceptives containing synthetic progestogens, such as the combined pill (eg Oralcon, or Marvelon), mini-pill (norethisterone, or levonorgestrel), contraceptive implants, or hormonal intrauterine systems (IUS). Additionally, some women taking certain types of body identical hormone replacement therapy (HRT), utrogestan (progesterone) may also experience side effects, but it is just less common. 


Factors like underlying mental health conditions, age, environmental stressors, and genetics may also influence sensitivity to progesterone.


Management Strategies


For those experiencing progesterone intolerance, several approaches can be considered

Switching to Body-Identical Progesterone : Options like Utrogestan, a micronized progesterone, may result in fewer side effects. Taking Utrogestan vaginally can reduce systemic absorption, helping to minimize side effects such as mood changes.

Considering Different Progestogen Forms : For some women, alternatives like the Mirena coil, which releases levonorgestrel directly into the uterus, may be better tolerated. Lower-dose intrauterine devices like the Jaydess or Moni Mirena can also be options for those who are sensitive to higher doses.

Exploring Alternative Progestogens: Interestingly, some individuals find they tolerate older synthetic progestins such as Provera (medroxyprogesterone) or norethisterone better than newer formulations, despite their traditional association with more side effects.

Newer Progesterone-Only Pills : Some women do better with progesterone-only contraceptives like Slinda (drospirenone) or Cerazette (desogestrel), which can provide a more stable hormonal environment.

Considering a Hysterectomy: In cases where progesterone intolerance is severe and significantly impacts quality of life, some individuals opt for a hysterectomy to remove the need for progesterone altogether.


If progesterone intolerance is affecting your ability to tolerate HRT or contraception, it’s important to explore different options with a healthcare professional to find the best approach for your individual needs.

Using Utrogestan Vaginally

How do you take progesterone vaginally — and why?

How:

Vaginal progesterone (like Utrogestan) is usually taken as a capsule inserted into the vagina using a clean finger, ideally at night before bed. The dose and number of days per month will depend on your hormone therapy and what you're using it for — your healthcare provider can guide this.


Why:


When taken vaginally, progesterone is absorbed directly through the vaginal wall into the uterus, where it’s needed to protect the endometrium (lining of the womb).


This route bypasses the liver and gut, leading to fewer systemic side effects like drowsiness, bloating, or mood swings.


It’s especially helpful for people who experience side effects when taking it orally or for those needing more targeted endometrial protection.

Vaginal utrogestan is not approved for endometrial protection

What does it mean that it's not “approved” or “licensed” for this use in menopause?

In many countries, Utrogestan (micronised progesterone) is only officially approved for oral use as part of menopausal hormone therapy.


Using it vaginally is considered “off-label” — this means it's not what the company got official approval for, even though there is clinical experience and evidence supporting its use this way.


Many menopause specialists and guidelines do use and recommend vaginal progesterone for endometrial protection — especially when oral use causes side effects — but it's important to understand that this is based on practical evidence and clinician judgement, not formal regulatory approval.


Hence it is really important that this isn't done without advice and discussion with a knowledgeable healthcare professional


A personalised programme

How I prescribe progesterone when used vaginally:

When patients prefer to use micronised progesterone (e.g. Utrogestan) vaginally — often due to side effects when taken orally — I still generally recommend the same dose as per oral guidelines, especially at first. That means:


  • 200mg daily for 12–14 days per month (for cyclical use)
  • 100mg daily continuously (for those not having periods).

Even though vaginal absorption is more direct, and some studies suggest that lower vaginal doses (even 100mg) may adequately protect the endometrium, we don’t have formal guideline dosing for this route. So, using the full 200mg provides reassurance, especially when the estrogen dose is higher or bleeding is irregular.


Once stable and symptom-free, if there are concerns about tolerance, cost, or long-term use, we may consider reducing the dose or frequency — but always with individualised risk–benefit discussion.