Progesterone calms the brain and promotes sleep. At the same time, progesterone seem to play a role in the mood symptoms of premenstrual dysphoric disorder (PMDD).
How can both things be true? The short answer is that progesterone is usually good for mood but can sometimes be bad.
Keep reading for the longer answer about progesterone and mood.
Contraceptive progestin drugs are bad for mood
Progestins are not the same as the body’s own progesterone, so they shouldn’t come into this conversation. Unfortunately, many doctors, journalists, and even scientists confuse progestins with progesterone and so say “progesterone is bad for mood” when they really mean progestins are bad for mood.
Contraceptive progestins such as levonorgestrel, drospirenone, and norethisterone have been linked with anxiety and depression, but mood symptoms from birth control are drug side effects, not PMS or PMDD.
Progesterone and the brain
For most women, the body’s own progesterone is soothing because it converts to a neurosteroid called allopregnanolone which calms GABA receptors in the brain.
Progesterone’s neurosteroid effect is why we feel sleepier during the luteal phase and pregnancy. It’s also why natural progesterone capsules are part of my “rescue prescription for perimenopause and menopause.” We don’t get the same soothing effect from contraceptive progestin drugs because progestins do not convert to allopregnanolone.
For a small number of women, allopregnanolone does something different at the GABA receptors. Instead of calming them, it produces intense anxiety and other mood symptoms, which is called premenstrual dysphoric disorder or PMDD.
Women with PMDD have the same amount of allopregnanolone as other women; they just respond to it differently. In particular, women with PMDD have a reduced ability to adapt to the normal ups and downs of allopregnanolone because their GABA receptors have a reduced ability to reshuffle their five subunits.
Normally, the subunits of the GABA receptors mix-and-match throughout the cycle to reconfigure the shape of the receptor and adjust its sensitivity to fluctuating levels of neurosteroids. It’s hormonal resilience in action.
If GABA receptors cannot reconfigure their shape or adapt to fluctuating progesterone, the result is what researcher Tory Eisenlohr-Moul calls “neurosteroid change sensitivity” producing the mood symptoms of PMDD. I am following the work of Dr. Eisenlohr-Moul with great interest, and if you want to hear more of Dr. Eisenlohr-Moul’s thoughts, please scroll down and read her very helpful comment under this blog post. (Shared on April 23 at 11:40 am.)
Neurosteroid sensitivity or PMDD affects about 1 in 20 women.
Conventional treatment of PMDD
Conventional treatment is:
- SSRI antidepressants to modulate GABA receptors, and/or
- hormonal birth control to shut down ovulation and progesterone.
SSRIs are a reasonable approach but there are a few considerations:
- SSRI antidepressants may increase the risk of osteoporosis. (See Dr. Eisenlohr-Moul’s comments about SSRIs in the comments below.)
- Contraceptive progestin drugs carry their own set of mood side effects.
- Women need ovulation and progesterone for long-term health. According to Professor Jerilynn Prior, “regular menstrual cycles with consistently normal ovulation…will prevent osteoporosis, breast cancer and heart disease.”
So, what else can be done? Is there a way to stabilize GABA receptors and therefore be able to tolerate the normal ups and downs of progesterone?
Natural treatment of PMDD
As it turns out, many of the established natural PMS treatments work on the GABA system and potentially on GABA receptors. They include:
- Reducing histamine and mast cell activation, which reduces histamine-induced mood symptoms and may alter GABA receptors. Histamine is the main driver of the swelling and irritability attributed to “estrogen dominance.” Histamine is one aspect of chronic inflammation which is a known driver of premenstrual mood symptoms. Read The Role of Histamine and Mast Cells in PMS and PMDD.
👉 Tip: For many of my patients, avoiding cow’s dairy is the simplest way to reduce a mast cell or histamine response. Another potentially beneficial effect of avoiding dairy is to reduce exposure to a casein-derived neuroactive peptide called BCM7, which affects levels of GABA.
- Magnesium, which supports a healthy GABA response and relieves PMS by “normalizing the action of progesterone on the central nervous system.” The best form is magnesium glycinate or bisglycinate because the amino acid glycine also calms GABA receptors.
👉 Tip: The therapeutic dose is 300 mg of elemental magnesium, so please read the label. Most magnesium capsules are about 100 mg magnesium per capsule, so the dose is three capsules.
- Vitamin B6 (pyridoxine), which assists in both the manufacture of GABA and the healthy clearance of histamine. The therapeutic dose is at least 50 mg pyridoxine or pyridoxal-5-phosphate, but I sometimes prescribe more to be taken during the days of mood symptoms. Consult your practitioner because long-term high-dose vitamin B6 can cause nerve damage.
👉 Tip: I get the best results with magnesium plus vitamin B6 plus the amino acid taurine (because taurine calms GABA receptors).
- Natural progesterone capsules because a higher external dose of progesterone can relieve the PMDD symptoms caused by fluctuating moderate levels of internal allopregnanolone. The explanation is an apparent “bimodal association between serum allopregnanolone concentration and adverse mood” which means that GABA receptors respond better to a higher steady-state level of allopregnanolone than they do to a lower fluctuating level.
For mood and sleep, 100 mg progesterone capsules (such as Prometrium) work better than progesterone cream because oral progesterone converts more readily to allopregnanolone.
The few studies that trialled natural progesterone for PMS used doses so large (400 to 1200 mg) that they caused side effects rather than benefits.
Natural progesterone is also good treatment for premenstrual migraines.
Milder PMS symptoms
Milder premenstrual symptoms (PMS) that occur only during the last few days of the cycle are not the same kind of neurosteroid sensitivity as PMDD. Instead, they are simply withdrawal from allopregnanolone. PMS responds to many of the treatments listed here as well as those in my histamine and PMS post.
Share your story about progesterone and PMDD.