Biomedical subjects

Marie Bixo

Publications and source records attributed to Marie Bixo.

15 recordsLinked to original sources

PubMed2006

Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone.

RATIONALE: Allopregnanolone effects on mood in postmenopausal women are unclear thus far. OBJECTIVES: Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment. MATERIALS AND METHODS: A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. Participants kept daily symptom ratings using a validated rating scale. Blood samples for progesterone and allopregnanolone analyses were collected during each treatment cycle. RESULTS: During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5-2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood. CONCLUSIONS: Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.

Administration, Oral↗

PubMed2006

Depression and anxiety during pregnancy and six months postpartum: a follow-up study.

AIMS: To investigate the relationship between antenatal and postpartum depression and anxiety and to explore associated maternal characteristics. METHODS: From a population-based sample of 1,555 women attending two obstetric clinics in Sweden, all women with an antenatal psychiatric diagnosis (n = 220) and a random selection of healthy women (n = 500) were contacted for a second assessment three to six months postpartum. The Primary Care Evaluation of Mental Disorders was used for evaluation on both occasions. RESULTS: Fewer cases of depressive and/or anxiety disorders were prevalent postpartum compared with the second trimester screening. Depression and/or anxiety were prevalent in 16.5% of postpartal women versus 29.2% of pregnant women. There was a significant shift from a majority of subthreshold diagnoses during pregnancy to full Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnoses during the postpartum period. A history of previous psychiatric disorder, living single, and obesity were significantly associated with a new-onset postpartum psychiatric disorder. The absence of a previous psychiatric disorder was significantly associated with a postpartum recovery of depression or anxiety. CONCLUSIONS: Depression and anxiety appear to be less common postpartum than during pregnancy.

Adult↗

PubMed2006

Patients with psychiatric disorders in gynecologic practice--a three year follow-up.

OBJECTIVE: Patients with depressive disorders are commonly encountered in gynecologic practice. The prevalence rates for depressive disorders have been reported to vary between 10 and 40% among patients consulting their gynecologist. The purpose of the current study was to study health care utilization by patients with a psychiatric disorder in the gynecologic setting during a three-year period after the initial diagnosis of depression and/or anxiety. STUDY DESIGN: In 1998 all scheduled and walk-in patients, at two gynecologic centers in northern Sweden during one month, were screened for prevalence of depression and anxiety disorders using the PRIME-MD system. Medical records for the period 16 December 1998 to 31 December 2001 have been reviewed. RESULTS: Patients diagnosed with any anxiety disorder made significantly more appointments to the gynecologist and were acutely hospitalized more often than control subjects. Both patients with any depressive or any anxiety diagnosis made significantly more visits to health care personnel other than the gynecologist and they received counseling by phone and/or letter significantly more often than patients in the control group. Furthermore, patients with depressive and/or anxiety diagnosis were also referred to other medical specialists more often than controls. CONCLUSION: The present study has indicated that gynecologic patients with depression and anxiety over a three-year follow-up period have an increased health care utilization with more frequent consultations and more frequent referrals.

Adult↗

PubMed2005

Endometrial safety and bleeding pattern during a five-year treatment with long-cycle hormone therapy.

OBJECTIVE: To determine compliance, the incidence of untoward effects, and endometrial safety in postmenopausal women treated with 3-month sequential hormone therapy for up to 5 years. DESIGN: A prospective, uncontrolled multicenter study of 129 women treated with 0.625 mg conjugated estrogens daily plus 10 mg medroxyprogesterone acetate for 14 days every third month. Endometrial biopsy samples were taken before the initiation of the study and then yearly during the next 5 years. Bleeding patterns were recorded. RESULTS: Upon completion of the first 12 months of treatment, 76 of 126 biopsied women (60%) had secretory endometrium. After 5 years, this finding was reversed in biopsy specimens completed by 59 women, among whom 32 (56%) had insufficient or atrophic endometrium. We did not find any hyperplasia when the biopsy specimen was taken according to the protocol. One endometrial cancer was found by biopsy after 12 months, but the subsequent hysterectomy showed no sign of cancer. Ultrasound determinations of mean endometrial thickness during therapy showed a thin endometrium (mean = 4 mm, range = 1-13 mm). Amenorrhea was reported by 6.2% of 129 women after 12 months of treatment. Among the 59 women who completed the study, 71.2% had regular bleeding patterns every third month, 25.4% reported amenorrhea, and 3.4% had irregular bleeding patterns. CONCLUSIONS: The addition of 10 mg of medroxyprogesterone acetate for 14 days every third month to treatment with 0.625 mg of conjugated estrogens daily was well tolerated, and was associated with high endometrial safety.

Biopsy↗

PubMed2005

Estradiol and the addition of progesterone increase the sensitivity to a neurosteroid in postmenopausal women.

The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT), using natural progesterone. A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment. Twenty six postmenopausal women with climacteric symptoms were administered HRT in a randomized, double blinded, placebo-controlled, crossover study. The women received 2 mg oral estradiol (E(2)) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle. Pharmacodynamic response to pregnanolone was assessed before treatment, and during the last week of each treatment cycle, by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV), saccade acceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. According to the daily symptom rating scales, patients were divided into two groups; one group who displayed a significant variance in negative mood symptoms during HRT (cyclicity) and one group with no cyclical changes in negative mood symptoms during treatment. During treatment with either E(2) alone or E(2)+progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values. The SEV, saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT. In conclusion, during treatment with either E(2) alone, or E(2)+progesterone, pregnanolone sensitivity was increased. Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT.

Adult↗

PubMed2005

Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone.

OBJECTIVE: To compare severity of negative mood and physical symptoms between women with different progesterone, allopregnanolone, and pregnanolone plasma concentrations during sequential Hormone Replacement Therapy (HRT) with vaginal progesterone suppositories. DESIGN: A randomized, placebo-controlled, double-blind, crossover study. METHOD: Postmenopausal women (n=36) with climacteric symptoms were treated with 2mg estradiol daily during three 28-day cycles. Vaginal progesterone suppositories with 400, 800 mg/day or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. Blood samples for progesterone, allopregnanolone, and pregnanolone radioimmunoassays were collected during each treatment cycle. RESULTS: Women were divided into three groups (low, medium, and high) based on plasma allopregnanolone concentration during progesterone treatment. The concentration of allopregnanolone in the medium group corresponds to the concentration seen during the mid luteal phase of the menstrual cycle. Within women with medium allopregnanolone concentration significantly more negative mood and physical symptoms were rated during progesterone treatment compared to treatment with unopposed estrogen or placebo. Between women significantly more negative mood symptoms were seen during progesterone treatment cycles with medium allopregnanolone concentration compared to cycles with low concentration. Plasma progesterone, allopregnanolone, and pregnanolone concentrations increased with increasing progesterone dose. Progesterone and allopregnanolone plasma concentrations increased 2h after vaginal administration of progesterone at 400 and 800 mg/day. CONCLUSION: Vaginal progesterone in sequential HRT causes negative mood, most likely mediated via allopregnanolone.

Administration, Intravaginal↗

PubMed2005

Evidence-based changes in term breech delivery practice in Sweden.

OBJECTIVE: Medical documentation on term breech delivery (TBD) advocates planned abdominal delivery based on evidence. The aim of the present study was to describe a change in TBD practice in Sweden following evidence-based documentation arguing in favor of TBD by cesarean section (CS). MATERIALS AND METHODS: The study was a population-based observational study based on data from the Swedish Medical Birth Register. Eligible subjects were all mothers with singleton children in term breech (TB) presentation born between 1999 and 2001 at > 36 weeks' gestational age. Data were processed, and subjects were subdivided into groups, according to mode of delivery. RESULTS: The CS rate increased from 75.3% in 1999 to 86.0% in 2001, due to an increase in planned abdominal deliveries. The change towards abdominal deliveries was more obvious for hospitals with fewer deliveries. While today, an increasing number of hospitals clearly have a non-selective CS policy, with a > 95% CS rate, others still deliver 30% of TB babies vaginally. CONCLUSION: In conclusion, the evidence-based recommendation for TBD has so far had considerable impact on Swedish obstetric practice.

Adult↗

PubMed2004

Effects of continuous combined conjugated estrogen/medroxyprogesterone acetate and 17beta-estadiol/norethisterone acetate on lipids and lipoproteins.

OBJECTIVES: Various estrogen/progestogen combinations used in hormonal replacement therapy (HRT) have been reported to influence lipid and lipoprotein fractions differently. This motivated a comparative study where the two continuous combined regimens most commonly used in Sweden during the 1990s have been studied regarding effects on lipid profile. METHODS: In a 1-year prospective, double-blind study, 62 post-menopausal women were randomized to conjugated estrogen (CE), 0.625 mg, and medroxyprogesterone acetate (MPA), 5 mg, or 17beta-estradiol (E2), 2 mg, and norethisterone acetate (NETA), 1 mg. Serum concentrations of lipids and lipoproteins were measured at baseline and after 1 year of treatment. RESULTS: Both treatment groups significantly lowered the lipoprotein(a) (Lp(a)) levels. The CE/MPA group showed no significant changes in total cholesterol (TC), high-density (HDL) and low-density lipoprotein (LDL), but a significant increase of triglyceride (TG) levels. The E2/NETA group developed a significant lowering of total cholesterol, HDL, and LDL, but no significant changes of TG levels. The magnitude of change in serum concentrations of total cholesterol, HDL and TG differed significantly between the two treatment groups. CONCLUSIONS: Continuous combined treatment with CE/MPA and E2/NETA equally lowered Lp(a), an important risk factor for cardiovascular disease in women. Apart from this, the two treatments produced different effects on lipids and lipoproteins, findings that are more delicate to interpret.

Cholesterol↗

PubMed2004

Neonatal outcome following maternal antenatal depression and anxiety: a population-based study.

The aim of this study was to determine neonatal outcomes among women who had depressive and anxiety disorders during the second trimester of pregnancy in a population-based sample. Participants were 1,465 women and their neonates born at two obstetric clinics in Sweden. The inclusion period for the women was October 2, 2000-October 1, 2001. The Primary Care Evaluation of Mental Disorders (PRIME-MD) classification system was used to evaluate mental disorders in the second trimester of pregnancy. For assessment of demographic characteristics, birth statistics, and birth-related complications, the medical records of the included women and their offspring were reviewed after delivery. The study results revealed no differences in neonatal outcome between women with antenatal depressive disorders and/or anxiety disorders and healthy subjects. The authors conclude that neonatal outcome did not deteriorate despite the women's impaired mental health during pregnancy.

Adult↗

PubMed2004

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).

Adult↗

PubMed2004

Implications of antenatal depression and anxiety for obstetric outcome.

OBJECTIVE: To investigate the obstetric outcome and health care consumption during pregnancy, delivery, and the early postpartum period in an unselected population-based sample of pregnant women diagnosed with antenatal depressive and/or anxiety disorders, compared with healthy subjects. METHODS: Participants were 1,495 women attending 2 obstetric clinics in Northern Sweden. The Primary Care Evaluation of Mental Disorders was used to evaluate depressive and anxiety disorders in the second trimester of pregnancy. To assess demographic characteristics, obstetric outcome, and complications, the medical records of the included women were reviewed. RESULTS: Significant associations were found between depression and/or anxiety and increased nausea and vomiting, prolonged sick leave during pregnancy and increased number of visits to the obstetrician, specifically, visits related to fear of childbirth and those related to contractions. Planned cesarean delivery and epidural analgesia during labor were also significantly more common in women with antenatal depression and/or anxiety. CONCLUSION: There is an association between antenatal depressive and/or anxiety disorders and increased health care use (including cesarean deliveries) during pregnancy and delivery.

Adult↗

PubMed2003

Point prevalence of psychiatric disorders during the second trimester of pregnancy: a population-based study.

OBJECTIVE: This study was undertaken to determine the point prevalence of psychiatric disorders during the second trimester of pregnancy in a population-based sample of pregnant women. STUDY DESIGN: Participants were 1795 consecutive pregnant women attending routine ultrasound screening at two obstetric clinics in Northern Sweden during 1 year. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used for evaluating. RESULTS: Overall, 1734 (96.6%) of the women filled in the PRIME-MD patient questionnaire. Psychiatric disorders were present in 14.1% of the women. Major depression was prevalent in 3.3% of patients and minor depression in 6.9% of patients. Anxiety disorders were encountered in 6.6% of patients. Women with psychiatric disorders displayed significantly more somatic symptoms and more pronounced fear of childbirth. Among diagnosed patients, only 5.5% had some form of treatment. CONCLUSION: The prevalence of mood and anxiety disorders in this unselected population of pregnant women was high and the majority of the women were found to be undiagnosed and untreated.

Adult↗

PubMed2003

Pathogenesis in menstrual cycle-linked CNS disorders.

That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.

Affect↗

PubMed2003

Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy.

Previous studies have indicated that the addition of progestins during sequential hormonal replacement therapy (HRT) causes negative mood and physical symptoms. History of premenstrual syndrome, type of progestin, and dose of progestin have thus far been shown to influence the progestin-induced adverse mood symptoms during HRT. The aim of this study was to compare adverse mood effects of two different doses of estradiol, in combination with a progestin, during postmenopausal HRT. Twenty-eight perimenopausal women were included in this randomized, double-blind, crossover study comparing 2- or 3-mg continuous estradiol, with an addition of 10 mg medroxyprogesterone acetate on d 17-28 during each treatment cycle. The main outcome measures were mood and physical symptoms kept on a daily rating scale. Together with the progestin, the higher dose of estrogen caused significantly more negative mood symptoms than the lower dose. Tension, irritability, and depressed mood were all significantly augmented during the progestin phase of cycles with 3 mg estradiol (P < 0.001). Physical symptoms also increased during the progestin phase of 3-mg estradiol cycles (P < 0.001), whereas positive mood symptoms were less affected. The only positive mood that changed with estrogen dose was friendliness, which decreased during the progestin phase of high estradiol cycles compared with cycles with lower estradiol (P < 0.05). Our conclusion is that an increase of the estrogen dose accentuates negative mood and physical symptoms during the progestin phase of sequential hormonal therapy.

Adult↗

PubMed1988

Human brain metabolism of morphine and naloxone.

The glucuronidation of morphine and naloxone was investigated in several regions of the human brain. Post-mortem brain tissue specimens were obtained from 19 patients 15 of whom had had cancer. With a few exceptions, all cancer patients had been treated with opiates during the terminal stage of their life. The glucuronide formation of morphine and naloxone was studied in vitro after incubation of the brain microsomal fraction with the substrate and uridine diphosphate glucuronic acid (UDPGA). The glucuronides were analyzed by high performance liquid chromatography. Glucuronidation of morphine and naloxone was catalyzed in 6 of the 19 investigated tissue specimens. The rate of formation of naloxone-3-glucuronide (N3G) exceeded that of the morphine-3-glucuronide (M3G). Morphine-6-glucuronide formation was found in only 2 specimens, in which the formation rate was 10% of the formation rate of M3G. When morphine and naloxone were present simultaneously at equal concentrations (3 mM), the N3G/M3G formation rate ratio increased compared to that when the 2 substrates were incubated one by one. Our findings are interesting from a clinical point of view since the pathways studied represent both bioactivation and inactivation steps in the metabolism of opioids.

Adult↗