Results of basic science studies demonstrate shared actions of endogenous neuroactive steroid hormones and drugs of abuse on neurotransmission. As such, premenstrual syndrome (PMS) may be associated with smoking, however, results from studies examining this relationship have been mixed. Following PRISMA guidelines, we extracted unique studies examining the relationship between smoking and PMS. We used the escalc () function in R to compute the log odds ratios and corresponding sampling variance for each study. We based quality assessment on the nature of PMS diagnosis and smoking estimation, confounding adjustment, participation rate, and a priori specification of target population. Our final sample included 13 studies, involving 25,828 study participants. Smoking was associated with an increased risk for PMS [OR = 1.56 (95% CI: 1.25–1.93), p < 0.0001]. Stratified by diagnosis, the effect size estimate was higher for Premenstrual Dysphoric Disorder (PMDD) [OR = 3.15 (95% CI: 2.20–4.52), p < 0.0001] than for PMS [OR = 1.27 (95% CI: 1.16–1.39), p < 0.0001]. We review some of the basic mechanisms for the observed association between smoking and PMS. Given nicotine's rewarding effects, increased smoking behavior may be a mechanism to alleviate affective symptoms of PMS. However, smoking may lead to worsening of PMS symptoms because nicotine has effects on neurocircuitry that increases susceptibility to environmental stressors. Indeed, prior evidence shows that the hypothalamic-pituitary-adrenal (HPA) axis is already sub-optimal in PMS, hence, smoking likely further deteriorates it. Combined, this complicates the clinical course for the treatment of both PMS and Tobacco Use Disorder in this population.

The regulation of DHEA-sulfate by steroid sulfotransferase (SULT) and steryl-sulfatase (STS) enzymes is a vital process for the downstream formation of many steroid hormones. DHEA-sulfate is the most abundant steroid hormone in the human body; thus, DHEA-sulfate and its hydrolyzed form, DHEA, continue to be evaluated in numerous studies, given their importance to human health. Yet, a basic question of relevance to the reproductive-age female population—whether the two steroid hormones vary across the menstrual cycle—has not been addressed. We applied a validated, multi-step protocol, involving realignment and imputation of study data to early follicular, mid-late follicular, periovulatory, and early, mid-, and late luteal subphases of the menstrual cycle, and analyzed DHEA-sulfate and DHEA serum concentrations using ultraperformance liquid chromatography tandem mass spectrometry. DHEA-sulfate levels started to decrease in the early luteal, significantly dropped in the mid-luteal, and returned to basal levels by the late luteal subphase. DHEA, however, did not vary across the menstrual cycle. The present study deep-mapped trajectories of DHEA and DHEA-sulfate across the entire menstrual cycle, demonstrating a significant decrease in DHEA-sulfate in the mid-luteal subphase. These findings are relevant to the active area of research examining associations between DHEA-sulfate levels and various disease states.

Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual dysphoric disorder (PMDD)—a debilitating affective condition thought to be marked by dysregulated stress processing and sensitivity to allopregnanolone. In the present study, women with PMDD (n = 17) and healthy controls (n = 18), who did not take medication, smoke, or consume illicit drugs, and who were free of other psychiatric conditions, participated in the Trier Social Stress Test, during which we measured the high frequency of the heart rate (HF-HRV) and allopregnanolone using ultra-performance liquid chromatography tandem mass spectrometry. Relative to their baseline, women who have PMDD, but not the healthy controls, experienced a reduction in HF-HRV during stress anticipation (p ≤ 0.05) and stress (p ≤ 0.01). Their recovery from stress was significantly delayed (p ≤ 0.05). Absolute peak HF-HRV change from baseline was significantly predicted by baseline allopregnanolone only in the PMDD group (p ≤ 0.01). The present study shows how an interaction between stress and allopregnanolone—which have both been separately implicated in PMDD—underlies PMDD expression.