I’d like to start this blog post with a little background on progesterone. Progesterone is fascinating and it affects a lot more than just the menstrual cycle. We are starting to understand just how big of an impact progesterone has, and the research project I am working on is beginning to show some of the potential applications of progesterone in medicine. These applications include improving recovery time after traumatic brain injury and strokes, as well as helping us understand postpartum depression (PPD) and premenstrual dysphoric disorder (PMDD).
PMDD is similar in mechanism with postpartum depression, although the exact mechanism is still being researched. Some research suggests a hormonal influence, as allopregnanolone, an offshoot neuroregulator of progesterone, modulates GABA, which is a neurotransmitter related to mood and anxiety. Too much GABA results in increased anxiety and mood related issues, so it is a logical conclusion that the drop in progesterone during the late luteal phase of the menstrual cycle would result in excess GABA and therefore symptoms of PMDD.
The article we discussed looked at PET scans of 12 women with and 12 women without a diagnosis of PMDD, taking scans during the follicular phase and the late luteal phase of their menstrual cycles. The women in the study were screened for two months with mood surveys and then taken in for a day of PET scans and blood/urine samples, once during the follicular phase and once during the late luteal phase, when the symptoms of PMDD would have begun. PMDD can affect certain brain functions, so they were using the PET scan to detect brain dysfunction, such as one study the article looked at that showed frontal lobe dysfunction associated with PMDD.
The hormone measurements didn’t show anything significant and PET scans showed increased cerebellum activity from follicular to late luteal phase in PMDD women only. The cerebellum has many GABA receptors, which is a possible explanation of this, but in journal club, we wondered if it is the lack of modulation after a drop in the progesterone, or if there is something going on with the number of receptors, such as perhaps some sort of diminished sensitivity to allopregnanolone.
In journal club, we discussed some of the problems we had with this study. Someone brought up the small sample size and too few collection times for samples and scan. The fact that only one cycle was measured impacted the study. Kate also mentioned that blood hormones are a less useful measure than salivary hormone measurements. Finally, while the article states that the cause of PMDD is an overactive cerebellum in women suffering from PMDD, they never really reach a definite reason for what is causing the increased action. Ultimately, the article would have benefitted from examining the hormones more closely and more often.
Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, & London ED (2011). Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biological psychiatry, 69 (4), 374-80 PMID: 21092938