In our population of older premenopausal women, we observed a strong positive relationship between BMI and the development of PMS. Women who were obese at baseline had significantly higher risks of developing PMS over 10 years of follow-up compared with lean women. BMI was also positively associated with risk of specific physical and emotional symptoms, including swelling of the extremities, backache, abdominal cramping, diarrhea/constipation, mood swings, and food cravings.
A limited number of previous studies have evaluated the relationship between adiposity and premenstrual symptoms and PMS, and to our knowledge, none of these studies have been prospective.3,6–10
Masho et al.7
found PMS prevalence to be 2.8-fold higher in obese women than underweight women (POR
2.8, 95%CI 1.1-2.7) in a population-based study. In the Study of Women's Health Across the Nation (SWAN),8
the prevalence of food cravings and bloating was significantly higher in overweight and obese women than in normal weight women and lower in underweight women. However, BMI was unrelated to other symptom groups, including anxiety and mood changes, cramps and back pain, breast pain, and headaches.
PMS is likely caused by a complex interaction of hormonal and neurochemical factors,5
and adiposity may increase risk through several mechanisms. Some studies have reported inverse associations between BMI and follicular phase estradiol levels in older premenopausal women,19–21
although others have not observed a relationship with follicular or luteal phase levels.22–24
In a recent study in our cohort, adult BMI was inversely associated with follicular and luteal phase total estradiol and luteal phase progesterone but unrelated to free estradiol levels21
; compared with women with BMI <20, women with BMI ≥30
had 39% lower follicular estradiol, 20% lower luteal estradiol, and 20% lower progesterone levels. Cyclic estrogen and progesterone fluctuations clearly contribute to the onset of PMS, as treatments suppressing ovulation are effective at preventing PMS symptoms.5
Whereas some evidence suggests that early luteal phase progesterone and perhaps estradiol levels may be higher in women with PMS compared with controls, women with PMS may also be more sensitive to cyclic hormone fluctuations, leading to more severe symptom experience.
Alternatively, obesity may alter neurotransmitter function through its effect on estrogen and progesterone. In some studies, PMS and premenstrual dysphoric disorder (PMDD) cases have demonstrated abnormalities of the serotonin, gamma-aminobutyric acid (GABA), and other systems compared with symptom-free controls.5
Estrogen enhances serotonin action by increasing synthesis, transport, reuptake and receptor expression, and postsynaptic responsiveness. Thus, it is plausible that lower estradiol levels associated with adiposity may lead to impaired serotonin function and contribute to the occurrence of PMS. This hypothesis is supported by clinical studies finding selective serotonin reuptake inhibitors (SSRls) to be effective at treating premenstrual mood symptoms, food cravings, appetite changes, and abdominal bloating.25
In our study, BMI was positively associated with many of these symptoms. Furthermore, the major progesterone metabolite, allopregnanolone, binds to GABA-A receptors and increases receptor sensitivity.5
Epperson et al.26
found follicular phase cortical GABA levels to be significantly lower in PMDD cases than in controls and to change in the opposite direction during the luteal phase. Thus, lower progesterone levels associated with obesity may impair GABA function and further contribute to the development of mood symptoms in PMS.
Increased adiposity may contribute to water-retention symptoms in PMS though dysregulation of the renin-angiotensin-aldosterone system (RAAS), leading to increased sodium and fluid retention.27
Estrogen stimulates the RAAS and increases fluid retention, whereas late luteal phase progesterone appears to counteract these effects.5,28
Finally, adiposity may be related to PMS by affecting vitamin D status. Obese individuals are at greater risk for vitamin D deficiency, as the main circulating vitamin D metabolite, 25-hydroxyvitamin D, is sequestered in adipose tissue. Vitamin D also plays a role in RAAS regulation.29
A previous study in our population found dietary intake of vitamin D to be inversely related to PMS incidence, although we were unable to assess the contribution of endogenously produced vitamin D.11
Additional studies evaluating the potential interplay of adiposity, sex steroid hormones, and neurotransmitters in PMS development are needed.
Our study has several limitations. As our participants were aged 27–44 at baseline, we were not able to prospectively evaluate the effect of adiposity and PMS at younger ages. Our results suggested that BMI at age 18 was not associated with PMS developing later in life (i.e., after age 27). Although adiposity at young ages may in fact not be associated with risk of PMS, it is also possible that women who were overweight or obese at age 18 developed PMS during adolescence or young adulthood. These women would have been ineligible for our study, as we excluded women who had already been diagnosed with PMS by the beginning of follow-up in 1991. Prospective studies of adolescent and young adult women are needed to further assess this relationship.
After adjusting for BMI, we did not find measures of central adiposity (e.g., waist circumference, waist/hip ratio) or weight cycling to be independently related to the development of PMS. These aspects of adiposity may indeed be unrelated to PMS, but we were only able to assess them in a subset of our study population; thus, our power for these analyses was relatively low. In addition, because we assessed only the presence of specific menstrual symptoms and not the severity of each, we could not identify which symptoms were most problematic to participants. Future large studies assessing multiple aspects of adiposity and severity of specific menstrual symptoms will be important to improving understanding of PMS etiology. Finally, as our study population was predominantly white, our findings may not be generalizable to women of other racial and ethnic groups, although it is unlikely that the physiological relationship between adiposity and PMS differs substantially between populations.
Strengths of our study include our prospective assessments of adiposity and aspects of weight change during the follow-up period. In addition, we collected information on a wide variety of additional factors potentially related to PMS occurrence and adiposity, including physical activity, smoking, and diet, and have taken these into consideration in our analysis. Finally, we used established criteria to define PMS cases13
and controls in order to identify women at the two extreme ends of the spectrum of menstrual symptom experience, which limited the likelihood of misclassification and maximized our ability to identify risk factors for moderate to severe PMS.