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.
Background: Although numerous motivations for vaping have been identified in adolescents, no study to date has examined a possible link between vaping and attitudes/behaviors that are associated with eating disorders in adolescent females. Examining this question in adolescent females is especially relevant given the higher prevalence of eating disorders in adolescent girls and women compared to adolescent boys and men.Methods: We recruited 299 girls (between 13 to 17 years old) via Facebook advertisement to complete a REDCap survey, which included the Electronic Cigarette Dependence Index (ECDI), Minnesota Eating Behavior Survey (MEBS), and demographic questions. Data were analyzed using nonparametric Spearman rank correlation test in R.Results: Electronic Cigarette Dependence Index (ECDI) scores were correlated with weight preoccupation (WP), binge eating (BE) and compensatory behavior (CB), but not body dissatisfaction (BD). The following were the results of Spearman correlation tests: (1) WP: rho = 0.13, p = 0.02; (2) BD: rho = 0.06, p = 0.28; (3) BE: rho = 0.15, p = 0.0095; (4) CB: rho = 0.021, p = 0.00027.Conclusion: The present study adds to the current literature examining motivations for e-cigarette use in adolescent girls. As eating disorders and e-cigarette dependence are significant public health concerns, our results highlight the need for intervention development.
Background: Allopregnanolone is one of the most studied neuroactive steroids; yet, despite its relevance to neuropsychiatric research, it is not known how it, as well as its ratio to progesterone, varies across all six subphases of the menstrual cycle. Two enzymes—5α-dihydroprogesterone and 5α-reductase—convert progesterone to allopregnanolone, and, based on immunohistochemical studies in rodents, the activity of 5α-reductase is considered the rate-limiting step in the formation of allopregnanolone. It is not clear, however, whether the same phenomenon is observed across to the menstrual cycle, and, if so, at what point this takes place. Methods: Thirty-seven women completed the study during which they attended eight clinic visits across one menstrual cycle. We analyzed their allopregnanolone and progesterone serum concentrations using ultraperformance liquid chromatography–tandem mass spectrometry, and we implemented a validated method to realign the data from the original eight clinic study visits, following which we imputed the missing data. Hence, we characterized allopregnanolone concentrations, and the ratio of allopregnanolone:progesterone at six menstrual cycle subphases: (1) early follicular, (2) mid-follicular, (3) periovulatory, (4) early luteal, (5) mid-luteal, and (6) late luteal. Results: There were significant differences in allopregnanolone levels between (1) early follicular and early luteal, (2) early follicular and mid-luteal, (3) mid-follicular and mid-luteal, (4) periovulatory and mid-luteal, and (5) mid-luteal and late luteal. We detected a sharp drop in allopregnanolone:progesterone ratio in the early luteal subphase. Within the luteal subphase, the ratio was the lowest in the mid-luteal subphase. Conclusions: Allopregnanolone concentrations are the most distinct, relative to the other subphases, in the mid-luteal subphase. The shape of the allopregnanolone trajectory across the cycle is similar to that of progesterone; however, the proportion of the two neuroactive steroid hormones is drastically different due to enzymatic saturation, which takes place at the start of the early luteal subphase, but continuing through, and peaking, in the mid-luteal subphase. Hence, the estimated activity of 5α-reductase decreases, but does not cease, at any point across the menstrual cycle.
It is not clear whether progesterone and estradiol associate with premenstrual food cravings, which significantly contribute to cardiometabolic adverse effects associated with obesity. We sought to investigate this question in the present study based on the prior literature showing a protective effect of progesterone on drug craving and extensive neurobiological overlaps between food and drug cravings. We enrolled 37 non-illicit drug- or medication-using women in the study to provide daily ratings of premenstrual food cravings and other symptoms across two-three menstrual cycles, based on which we classified them as premenstrual dysphoric disorder (PMDD) or control participants. In addition, the participants provided blood samples at eight clinic visits across the menstrual cycle. We aligned their mid-luteal progesterone and estradiol using a validated method which relies upon the peak serum luteinizing hormone and analyzed estradiol and progesterone using ultraperformance liquid chromatography tandem mass spectrometry. Hierarchical modeling, adjusted for BMI, showed a significant inverse effect of progesterone (p = 0.038) but no effect of estradiol on premenstrual food cravings. The association was not unique to PMDD or control participants. Results of research to date in humans and rodents showing that progesterone has dampening effects on the salience of the reinforcer translate to premenstrual food cravings.
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