What causes PMDD?
PMDD is complex and the exact cause is not fully understood. Potential contributors include generic, biological and psychosocial factors.
Genetics
There is evidence to suggest that PMDD is heritable (ranging from 30-80%), indicating a potential link between genetic factors and an increased risk of developing the disorder. This connection has been shown in family, twin studies and studies looking at specific genes variations.
Biological (Hormones and hormonal sensitivity)
The way in which hormones produced by the ovaries affect a person's symptoms is not completely understood, but there are a few theories. One theory is that the hormones can affect the way genes are activated, which can impact how the body functions. Another theory is that hormones can have quick effects on the body that don't involve genes, but still change how cells work.
The leading hypothesis is that PMDD is caused by a hormone sensitivity in the central nervous system (CNS). BUT the current understanding of PMDD suggests that it's not simply a matter of the brain being more or less sensitive to progesterone or other hormones. Rather, it's thought that the brain's response to specific hormones, such as progesterone metabolites like allopregnanolone, may be altered in individuals with PMDD.
Progesterone and its metabolite ALLO: Allopregnanolone (ALLO)
ALLO is a metabolite of progesterone that can help to enhance the effects of GABA in the brain. GABA is a neurotransmitter that has a calming effect on the brain. Women with PMDD show some evidence of altered GABA receptor response (decreased receptor sensitivity) to ALLO, which may explain why they have do not experience the calming effects of GABA compared to individuals who do not have PMDD.
Some studies suggest that in women with PMDD, the levels of allopregnanolone are lower than in women without PMDD during the luteal phase of the menstrual cycle. This suggests that there may be a problem with the synthesis or metabolism of allopregnanolone in these individuals, which could lead to lower levels of the hormone binding to GABA receptors in the brain. Other studies have found that the sensitivity of the GABA receptors themselves may be altered in women with PMDD, which could affect how well allopregnanolone is able to bind to and activate these receptors.So, the exact mechanism underlying PMDD is complex and likely involves multiple factors, including alterations in the synthesis, metabolism, and binding of hormones like allopregnanolone, as well as changes in the sensitivity of GABA receptors in the brain.
Estrogen, serotonin, BDNF (Brain derived neurotrophic factor)
Research also seems to suggest that there are alterations in other hormones and neurotransmitters that may play a role in the development of PMDD.
Estrogen and serotonin affect multiple systems that regulate mood and behavior. Estrogen and serotonin interactions are thought to be involved in development of PMDD however not fully understood. It seems as though estrogen has an effect on serotonin expression. In addition, they have found lower levels of serotonin in the luteal phase that may explain some of the symptoms experienced in the second half of the cycle.
BDNF is a protein that plays a crucial role in promoting the growth and development of neurons, and is important for maintaining healthy brain function. It has neuroprotective properties and has been linked to the prevention of neurodegenerative diseases. However, women with PMDD have been found to have lower levels of BDNF during the luteal phase compared to women without PMDD
Psychosocial (stress, trauma)
Individuals who have experienced significant stress and trauma in their lives may be more likely to develop PMDD. Some studies have found a link between trauma history, including emotional and physical abuse, and the severity of PMDD symptoms. However, other studies have not found a significant difference between women with PMDD and healthy controls in terms of abuse history. Researchers are now trying to understand the underlying mechanisms that connect stress and PMDD, with a focus on the hormone ALLO. Although ALLO normally increases in response to acute stress, women with PMDD do not show this typical response. Studies in animals suggest that chronic stress can blunt ALLO levels, and researchers are exploring whether this may also be true in humans. Understanding these mechanisms may help researchers develop new treatments for PMDD.
Immune and inflammation
Depression has been linked to inflammation and immune system dysfunction, and while PMDD and depression are different, inflammation may play a role in the development of PMDD. During the luteal phase, there is an increased number of proinflammatory molecules.
As you can see the causes of pmdd are complicated and still under investigation. it is likely that it is not one single cause and a combination genetic, hormonal, and environmental factors such as stress and trauma. More research is needed to fully understand the underlying mechanisms and risk factors associated with PMDD, which could ultimately lead to improved diagnosis and treatment options for those affected by this condition.
More to come on treatment options and resources! :)
References:
Premenstrual Dysphoric Disorder: Epidemiology and Treatment
Update on Research and Treatment of Premenstrual Dysphoric Disorder
Evidence-based treatment of Premenstrual Dysphoric Disorder: a concise review