Mats Löfgren

Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

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.

Patient accept questionnaires integrated in clinical routine: a study by the Swedish National Register for Gynecological Surgery

Background. In 1996, the Swedish National Register for Gynecological Surgery started to collect pre‐ and postoperative information on patients using questionnaires given out as part of routine medical care. The information is used in providing clinical care to the patient and for quality assessment.

Effects in vitro of progesterone and two 5α‐reduced progestins, 5α‐pregnane‐3,20‐dione and 5α‐pregnane‐3α‐ol‐20‐one, on contracting human myometrium at term

Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5α‐reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5α‐reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5α‐reduced metabolite, 5α‐pregnane‐3,20‐dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5α‐pregnane‐3α‐ol‐20‐one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p<0.05). Similar results have been reported previously in the literature; 5α‐pregnane‐3α‐ol‐20‐one showed the same tendency though not significant at the 5% level. 5α‐pregnane‐3,20‐dione evidently reduced the contraction frequency after 10 min of exposure (p<0.05). None of the substances affected the duration of the contraction. These 5α‐reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

Hysterectomy and incontinence : a study from the swedish national register for gynecological surgery

Background. Hysterectomy is one factor that has been suggested to be a risk factor for developing stress incontinence. In Sweden, with a population of 8.86 million, a national register was set up in 1997 in order to have data for assessing the quality of gynecological surgery for benign disorders. Methods. Data in the Swedish national register for gynecological surgery during the period 1997–2002 were investigated. Surgical methods compared during this time period were: total hysterectomy (abdominal/laparoscopic, n=198/116), subtotal hysterectomy (abdominal/laparoscopic, n=163/86), and total hysterectomy (vaginal/laparoscopic assisted vaginal, n=265/7). Patients who underwent endometrial destruction (endometrial ablation, endometrial balloon treatment, n=187) were used as a control group. Only patients with no preoperative complaints were included. Outcome measures were answers to subjective questions asked pre‐ and postoperatively regarding urinary problems and incontinence. Results. De novo symptoms of stress incontinence, urgency and urgency incontinence, and/or mixed incontinence were noted in all groups. No differences were found among the groups. Conclusion. Factors other than hysterectomy should be discussed causing stress incontinence in women.

Getting informed consent from patients to take part in the clinical training of students: randomised trial of two strategies

Getting informed consent from patients to take part in the clinical training of students : randomised trial of two strategies

Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro

Objective: To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. Methods: Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 &mgr;g/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 × 7.5‐mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 &mgr;g/mL progesterone, 5 &mgr;g/mL progesterone plus 10 mU/mL oxytocin, 5 &mgr;g/mL progesterone plus 100 mU/mL oxytocin, 10 mU/mL oxytocin, and 100 mU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. Results: The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 mU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 mU/mL oxytocin alone, compared to buffer. Conclusion: Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin. (Obstet Gynecol 1993;82:532‐8)

No difference in length of hospital stay between laparoscopic and abdominal supravaginal hysterectomy – a preliminary study

Background. Although a number of well‐designed studies have concluded that laparoscopic hysterectomy is associated with less postoperative pain, reduced hospital stay, and shorter periods of sick leave, thus far, studies on the perioperative and postoperative outcomes of laparoscopic supravaginal hysterectomy (LSH) versus abdominal supravaginal hysterectomy (ASH) are lacking. By applying multimodal intervention program for the postoperative care of patients, the primary aim of the current study was to compare length of hospital stay, time to convalescence, and long‐term patient satisfaction between LSH and ASH. Method. The study was conducted at the departments of Obstetrics and Gynecology, Skellefteå Hospital and Lycksele Hospital. Forty‐seven consecutive women scheduled for supravaginal hysterectomy were randomly assigned to LSH or ASH. Perioperative and postoperative parameters were compared between the two groups. Results. The length of the postoperative hospital stay did not differ between patients undergoing LSH and ASH, but the number of disability days was greater in the ASH group. The operating time was significantly longer in the LSH group compared with the ASH group, whereas the estimated perioperative bleeding was greater in the ASH group. At the 6‐month follow‐up, 87.0% of patients in the ASH group and 91.3% in the LSH group were satisfied or very satisfied with the overall result of the surgical procedure. Conclusion. The present study has indicated that by applying a multimodal intervention program for the postoperative care of patients undergoing supravaginal hysterectomy, the surgical procedure per se is of less importance than generally considered for the length of postoperative hospital stay and long‐term patient satisfaction.

High progesterone is related to effective human labor: Study of serum progesterone and 5α-pregnane-3,20-dione in normal and abnormal deliveries

Background. The role of progesterone levels during human labor is unclear.

Decrease in Serum Concentration of 5α‐Pregnane‐3,20‐Dione Prior to Spontaneous Labor

Serum 5α‐pregnane‐3,20‐dione (5αDHP) and progesterone (P) concentrations before spontaneous labor were studied in 13 women whose pregnancy and delivery were uncomplicated. Blood samples were drawn twice weekly from the 36th week of gestation up to the onset of spontaneous labor. P and 5αDHP values were analysed by applying RIA methods. Mean serum 5αDHP concentrations declined significantly during the last week of pregnancy, from 135±12 nmol/l 5 days prior to spontaneous labor, to 111 ±10 nmol/l on the day spontaneous labor started (p < 0.005). No significant changes in progesterone concentration occurred during the observation period. These results suggest a change in 5aDHP production preceding the onset of spontaneous labor.