CASE: Why might micronised progesterone (Utrogestan) be considered in someone with PMDD despite a Mirena being in place?

PMDD is not usually caused by abnormal hormone levels. It is better understood as increased brain sensitivity to normal ovarian hormone fluctuations, especially progesterone and its neuroactive metabolites.

A Mirena provides levonorgestrel mainly within the uterus. It is excellent for contraception and endometrial protection, but it does not reliably suppress ovulation in all users. Therefore, cyclical ovarian hormone changes may continue, and PMDD symptoms may persist despite a Mirena.

It is also important that synthetic progestins and micronised progesterone are not the same. Levonorgestrel, norethisterone, medroxyprogesterone, dienogest and micronised progesterone differ in receptor activity, metabolism and central nervous system effects. Poor tolerance of one progestogen does not automatically predict poor tolerance of another.

Micronised progesterone is body-identical progesterone. When taken orally, it is metabolised into neuroactive steroids including allopregnanolone, which acts on GABA-A receptors. This may influence sleep, anxiety, stress responsiveness, emotional regulation, pain perception and nervous system arousal.

For some people, this can have a calming and stabilising effect. For others, especially those with progesterone sensitivity, symptoms may worsen. For this reason, I would not view micronised progesterone as a universal PMDD treatment, but as a carefully monitored therapeutic trial in selected patients.

This may be particularly relevant in patients with neurodivergence, including ADHD or autism, where PMDD and severe cyclical mood symptoms appear more common. Clinically, these patients may respond strongly to hormonal interventions — sometimes very positively, sometimes poorly — so a reversible monitored trial can be informative.

The presence of a Mirena does not automatically prevent the use of additional systemic progestogens. Additional progestogens are commonly used alongside Mirena for conditions such as endometriosis, adenomyosis, pelvic pain, menstrual suppression and abnormal bleeding. The key question is whether there is a clear rationale, acceptable safety profile, therapeutic goal and monitoring plan.

Micronised progesterone has a comparatively favourable safety profile compared with many synthetic progestins, including less concerning cardiovascular, metabolic, thrombotic and breast safety signals in menopause literature. It has also not shown the same meningioma risk signal seen with some high-dose synthetic progestogens, although long-term PMDD-specific data remain limited.

I would discuss uncertainty openly and monitor for benefit in sleep, emotional regulation, pain, distress, function, work, relationships and overall quality of life. If symptoms worsen, it should be stopped.

In summary, micronised progesterone is not a guideline-first treatment for PMDD. However, in selected patients where PMDD persists despite Mirena, other options have been poorly tolerated, and there is a clear monitoring plan, it may be a biologically plausible, reversible and relatively low-risk therapeutic trial.

I wrote this for a colleague, and thought you may find it interesting

- Dr Sam