Allopregnanolone: definition and meaning
Allopregnanolone is a neurosteroid made from progesterone, in the ovaries and in the brain. It acts on GABA-A receptors, the brain's main calming system, and usually has a relaxing, anti-anxiety effect. Levels rise after ovulation and fall before a period. In people with PMDD, the brain appears to react unusually to these normal changes.
What allopregnanolone does
After ovulation, the corpus luteum makes progesterone, and some of it is turned into allopregnanolone. In most people this is mildly soothing, a bit like the brain's own version of a calming medicine. Levels also rise hugely in pregnancy and drop sharply after birth.
Why researchers link it to PMDD
Hormone levels in people with PMDD are usually normal. The difference seems to be sensitivity. Research suggests that in PMDD the GABA-A receptors do not adapt smoothly to rising and falling allopregnanolone, so the same hormone change triggers anxiety, irritability or low mood instead of calm.
- Symptoms track the luteal phase, when allopregnanolone is changing.
- Stopping ovulation (and so the luteal rise) often eases symptoms.
- Early trials of a drug that blocks the effect of allopregnanolone (sepranolone) reduced some PMDD symptoms, though it is not an approved treatment.
- Brexanolone and zuranolone, drugs related to allopregnanolone, are approved in the US for postpartum depression.
What this means for you
The research supports what many people feel: premenstrual mood changes are biological, not a character flaw. Current PMDD treatments include SSRIs, ovulation-suppressing options and talking therapy. Read more in PMDD treatment and PMS vs PMDD.
If premenstrual mood changes bring thoughts of harming yourself, please reach out now: call your local emergency number, or in the US call or text 988. In the UK, Samaritans are on 116 123.
Frequently asked questions
Can I take allopregnanolone for PMS?
No. It is not available as a PMS treatment. Related medicines are approved only for postpartum depression.
Is low allopregnanolone the cause of PMDD?
Not exactly. Most studies find normal levels; the issue seems to be how the brain responds to changes in them.
Sources
- B盲ckstr枚m T et al. A randomized, double-blind study on efficacy and safety of sepranolone in premenstrual dysphoric disorder. Psychoneuroendocrinology (2021)
- Schweizer-Schubert S et al. Steroid hormone sensitivity in reproductive mood disorders: the role of the GABA-A receptor complex. Front Med (2021)
- Schmidt PJ et al. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. NEJM (1998)
This page is for information only and isn鈥檛 medical advice. If something worries you, please talk to a doctor.
Keep reading
What is premenstrual dysphoric disorder (PMDD)?PMDD (premenstrual dysphoric disorder) is a severe, cyclical mood condition in the week or two before a period. Symptoms, diagnosis and treatment options.PMDD: premenstrual dysphoric disorder, explained kindlyPMDD is a severe, cyclical mood condition tied to your period. What it is, why it happens, how it's diagnosed, what treatment helps, and where to get support.
PMDD treatment: options to discuss with your doctorPMDD treatment explained: SSRIs including luteal-phase dosing, the drospirenone pill, CBT, GnRH options and lifestyle steps, plus how to find the right care.
Progesterone: definition and meaningProgesterone is the hormone made after ovulation that prepares the uterus for pregnancy. Its role in the luteal phase, PMS, mood, sleep and temperature.
Serotonin: definition and meaningSerotonin is a brain chemical that helps regulate mood, sleep and appetite. How falling hormones before a period may affect it, and its link to PMS and PMDD.