Inger Sundström Poromaa

Measurement of direct ethanol metabolites suggests higher rate of alcohol use among pregnant women than found with the AUDIT—a pilot study in a population-based sample of Swedish women

OBJECTIVES The objective of the study was to investigate whether biomarkers of alcohol consumption would provide additional information to the use of a validated alcohol questionnaire in pregnant women. STUDY DESIGN One hundred three pregnant women were included in the study. The women completed the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and a urine and hair sample was collected. The urine samples were used for determination of ethyl glucuronide (EtG) and ethyl sulfate and the hair samples for EtG and fatty acid ethyl esters (FAEE). RESULTS Twenty-six women (25.2%) were identified as possible alcohol consumers by the combined use of AUDIT and direct ethanol metabolites. Seven subjects had EtG or FAEE levels in hair highly suspicious of heavy drinking, but only 1 of these were positive according to the AUDIT questionnaire CONCLUSION The combined use of the AUDIT questionnaire and direct ethanol metabolites appear to identify more potential alcohol consumers among pregnant women than does the sole use of the AUDIT questionnaire.

Postoperative infections and antibiotic prophylaxis for hysterectomy in Sweden: a study by the Swedish National Register for Gynecologic Surgery.

Aim.  The purpose of the study was to evaluate the current use of antibiotic prophylaxis, the rate of postoperative infections, and risk factors for postoperative infections in patients undergoing elective hysterectomy for non‐malignant pathology.

Altered sensitivity to alcohol in the late luteal phase among patients with premenstrual dysphoric disorder

BACKGROUND Affective disorders, and possibly also premenstrual dysphoric disorder (PMDD) are risk factors for alcohol abuse in women. Although the majority of prior studies have indicated that alcohol sensitivity does not differ between menstrual cycle phases, patients with PMDD have thus far not been studied. METHODS We have evaluated the functional sensitivity to a low dose of alcohol in 12 women with and 12 women without PMDD in the mid-follicular and late luteal phases of the menstrual cycle, by comparing the effects of an intravenous alcohol infusion on a number of saccadic eye movement measures, including saccadic eye velocity (SEV), saccade deceleration, and self-rated levels of intoxication. RESULTS PMDD patients displayed blunted SEV (p<0.01) and saccade deceleration responses (p<0.01) to alcohol infusion in the late luteal phase compared to the mid-follicular phase. Control subjects, on the other hand, did not change their SEV or saccade deceleration responses to alcohol between cycle phases. CONCLUSION These findings are compatible with altered saccadic eye movement sensitivity in response to alcohol among PMDD patients, particularly in the late luteal phase of the menstrual cycle.

Allopregnanolone and pregnanolone are produced by the human corpus luteum.

Using a dispersed human luteal cell culture model, progesterone, allopregnanolone and pregnanolone release following treatment by incremental doses of human chorionic gonadotrophin (hCG) were evaluated. Corpus luteum tissues, obtained from 48 healthy women scheduled for benign surgery, were grouped according to luteal age and tissue concentration of allopregnanolone and pregnanolone was determined. The mRNA expression of 5alpha-, and 5beta-reductase and 3alpha-HSOR mRNA expressions were evaluated in corpora lutea from the late luteal phase. Allopregnanolone concentrations in corpus luteum tissue were consistently about three- to four-fold higher than pregnanolone levels. Allopregnanolone tissue concentrations significantly decreased between early- and late-luteal phase, p<0.05. When exposed to hCG, progesterone output from freshly obtained human corpora lutea cells was two- three-fold increased compared to control levels. With 0.1U/ml hCG a two-fold increase in allopregnanolone levels were noted, whereas pregnanolone levels were increased by approximately 40%. Furthermore, the mRNA of 5alpha-, 5beta-reductase and 3alpha-HSOR mRNA were all expressed in human corpus luteum. In conclusion, the neurosteroids allopregnanolone and pregnanolone are produced in the human corpus luteum and their release is stimulated by trophic hormone.

Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

Adverse mood symptoms with oral contraceptives

In spite of combined oral contraceptives (COCs) having been available for more than 50 years, surprisingly little is known about the prevalence of truly COC‐related adverse mood symptoms and about the underlying biological mechanisms of proposed changes in mood and affect. Precise estimates of COC‐related adverse mood symptoms are not available due to the lack of placebo‐controlled trials. In prospective trials the frequency of women who report deteriorated mood or deteriorated emotional well‐being varies between 4 and 10%, but it can be assumed that the causal relation in these prevalence rates is overestimated. Adverse mood symptoms and somatic symptoms are most pronounced during the pill‐free interval of the treatment cycles, but whether extended COC regimens would be more favorable in this respect is not known. COCs with anti‐androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms than progestagens with a more androgenic profile. Available data suggest that lower doses of ethinylestradiol could be beneficial.

Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding

Depression and anxiety are common health problems affecting women, particularly during the reproductive years. Major depression is two to three times as common in women than in men. Neuroendocrine factors are likely to contribute to this overall increased risk for developing mood disorders in women, and the neuroendocrine influence is most obviously seen in women with premenstrual dysphoric disorder (PMDD) as these women experience depressed mood and anxiety premenstrually only during ovulatory cycles. Moreover, dysfunction of serotonergic transmission has been regarded as an important mechanism in several psychiatric disorders and ovarian steroids have been shown to profoundly influence the activity of the serotonergic system. Given these facts, the purpose of this study was to examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide ([3H]LSD) to the platelet 5-HT2A receptor are influenced by the cyclical changes in circulating estradiol and progesterone that occur during the menstrual cycle. We examined 28 healthy women, without oral contraceptives and with regular menstrual cycles. In the late follicular phase, Bmax for [3H]paroxetine binding was significantly higher than in the ovulatory (p<0.01), early luteal phase (p<0.05) and mid-luteal phase (p<0.01). Bmax for [3H]LSD binding was significantly higher in the early follicular phase and the early luteal phase compared to the mid-luteal phase (p<0.001 and p<0.05, respectively). In the early follicular phase and the ovulatory phase, significant correlations between estradiol serum concentrations and Kd for [3H]paroxetine were obtained (p<0.001, respectively). In the luteal phase, significant inverse correlations between progesterone as well as estradiol serum concentrations and Kd for [3H]LSD binding were found (p<0.05, respectively).

Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome

Background. Neurosteroids such as allopregnanolone and pregnanolone are suggested to be of importance for the pathophysiology of premenstrual dysphoric disorder. The aim of this study was to investigate whether the luteal-phase serum concentrations of these neurosteroids are associated with improvement of premenstrual symptoms in 12 women with severe premenstrual syndrome after treatment with low-dose gonadotropin-releasing hormone agonist and placebo. Methods. Daily ratings for mood and physical symptoms were made prior to treatment and throughout the study. Serum progesterone, allopregnanolone and pregnanolone were assessed in the luteal phase (cycle day −9 to cycle day −1). Based on their symptom ratings, subjects were grouped as either buserelin responders (n = 6) or placebo responders (n = 6). Results. Buserelin responders displayed decreased levels of allopregnanolone (p < 0.05) and progesterone (p < 0.05) in parallel with improvement of symptoms. During the placebo treatment, the placebo responders had lower serum allopregnanolone concentrations than buserelin responders (p < 0.05). This was associated with improvement in symptoms compared with pre-treatment ratings. Conclusion. Treatment response, whether induced by buserelin or placebo, appears to be associated with a decrease in allopregnanolone concentration.

No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls

BACKGROUND Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue. METHODS Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR. RESULTS Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost. CONCLUSIONS Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS)

BackgroundProgesterone receptor membrane component 1 (PGRMC1) is a member of a progesterone-binding complex implicated in female reproduction. We aimed i) to determine the natural expression of PGRMC1 in peripheral nucleated blood cells throughout the menstrual cycle and ii) to investigate any association between PGRMC1 levels in leukocytes and conditions characterized by reduced fertility.MethodsWe analyzed PGRMC1 expression in peripheral leukocytes from 15 healthy cycling women over four weeks. Additionally, we determined PGRMC1 levels in samples from patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) as well as in healthy postmenopausal women and male controls. The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.ResultsPGRMC1 levels did not vary significantly throughout the menstrual cycle. We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.ConclusionThis study suggests that reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function.