Biomedical subjects

Sigrid Nyberg

Publications and source records attributed to Sigrid Nyberg.

13 recordsLinked to original sources

PubMed2006

Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea.

OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. DESIGN: Cross-sectional study. SETTING: Umeå University Hospital, Umeå, Sweden. PATIENTS: Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. RESULTS: Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. CONCLUSION: The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.

Adrenocorticotropic Hormone↗

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

Psychophysically determined thresholds for thermal perception and pain perception in healthy women across the menstrual cycle.

OBJECTIVES: Several studies have indicated changes in sensation and/or pain sensitivity among women across the menstrual cycle, but the pattern of the changes varies considerably. One reason for the reported discrepancies could reside in lack of biochemical definition of menstrual cycle phase. The aim was to quantify temperature and temperature pain thresholds at biochemically defined stages of the menstrual cycle. METHODS: Nineteen healthy women were included in the study. Temperature and temperature pain thresholds were evaluated by quantitative sensory testing, performed at 3 occasions during the menstrual cycle (early follicular phase, late follicular phase, and mid-luteal phase). At each test session, serum concentrations of estradiol and progesterone were assessed. RESULTS: Thermal cold perception threshold at the mammilla was significantly lower in the late follicular and mid-luteal phases, compared with the early follicular phase (P<0.05, respectively). For the remaining test sites, no cycle related differences in thermal perception or thermal thresholds could be documented. CONCLUSIONS: The present study has indicated no major changes in thermal pain thresholds related to phase of the menstrual cycle for the tested locations, although thermal cold perception threshold at the mammilla was a significantly lower in the late follicular and mid-luteal phases, compared with the early follicular phase. The findings of the present study further underlines the need for strict criteria for menstrual cycle phase when studying pain sensitivity in relation to hormonal events in women.

Adult↗

PubMed2005

Pharmacokinetic and behavioral effects of allopregnanolone in healthy women.

RATIONALE: The behavioral effects of allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) in women are not known. OBJECTIVE: Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABAA receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women. METHODS: Ten healthy women were given three increasing intravenous doses of allopregnanolone in the follicular phase of the menstrual cycle. Saccadic eye movement parameters and visual analogue scales of sedation were used to evaluate the behavioral response of allopregnanolone. Repeated blood samples for analyses of allopregnanolone were drawn throughout the study day. RESULTS: Exogenously administered allopregnanolone decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid. CONCLUSION: The behavioral effects of allopregnanolone are similar to that of its 5beta-stereoisomer, pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one). Apart from fatigue and mild nausea, allopregnanolone given in a cumulative dose of 0.09 mg/kg did not have any adverse effects.

Adult↗

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

The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls.

BACKGROUND: Neurosteroids have been proposed to play an important role in the interaction between alcohol and GABA(A) receptors and for the symptomatology of premenstrual dysphoric disorder (PMDD). The primary aim of this study was to investigate possible alcohol-induced changes in allopregnanolone serum concentrations across different menstrual cycle phases in women with severe premenstrual syndrome (PMS) and controls. METHODS: The allopregnanolone and cortisol responses to a low-dose of alcohol were evaluated in 14 women with and 12 women without severe premenstrual syndrome in the follicular and late luteal phases. The effect of a 30-min intravenous alcohol infusion (0.2 g/kg) on allopregnanolone and cortisol serum concentrations was compared to placebo, and compared between cycle phases and groups. Blood samples for measuring allopregnanolone were taken at baseline 25, 55, and 75 min after the start of the alcohol infusion. RESULTS: In the late luteal phase, the alcohol infusion decreased allopregnanolone levels, compared to baseline levels as well as to placebo. The difference in allopregnanolone levels between alcohol and placebo was evident 25 min (P < 0.01), 55 min (P < 0.01), and 75 min (P < 0.05) after start of the infusion. There was no change in allopregnanolone levels during the alcohol infusion in the follicular phase. Also, no difference in alcohol-induced allopregnanolone response between PMS patients and control subjects was detected. Cortisol levels declined during both the placebo and alcohol infusion, but did not differ with respect to which infusion had been given. CONCLUSION: During the late luteal phase, independent of PMS diagnosis, the low-dose alcohol infusion resulted in decreasing peripheral allopregnanolone levels.

Adult↗

PubMed2004

No difference in responsiveness to a low dose of alcohol between healthy women and men.

The purpose of the current study was to examine gender-related differences in alcohol responsiveness by comparing the effect of a low-dose intravenous alcohol infusion upon saccadic eye movements, self-rated sedation and intoxication scores. The functional sensitivity to a low dose of alcohol in 12 healthy women and 12 healthy men was evaluated by comparing the effects of an intravenous alcohol infusion on a number of saccadic eye movement measures, including saccadic eye velocity (SEV), saccade latency, saccade accuracy, saccade deceleration and self-rated levels of intoxication and sedation. The infusion of a low dose of alcohol induced a decrease in SEV and increased saccade deceleration and self-rated scores of intoxication in both males and females. Saccade accuracy was also significantly deteriorated by alcohol in both groups. The alcohol infusion did not induce any main gender-related differences in the saccade or visual analogue scale measurements. According to the findings of the present study, no gender differences in the responsiveness to a low-dose alcohol infusion were found.

Adult↗

PubMed2004

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.

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↗

PubMed2003

Progesterone effects during sequential hormone replacement therapy.

OBJECTIVE: The aim was to investigate the effect on mood and the physical symptoms of two dosages of natural progesterone and a placebo in postmenopausal women with and without a history of premenstrual syndrome (PMS). DESIGN: A randomized, placebo-controlled, double-blind, crossover study was performed. METHOD: Postmenopausal women (n=36) with climacteric symptoms were recruited. They received 2 mg estradiol continuously during three 28-day cycles. Vaginal progesterone suppositories with 800 mg/day, 400 mg/day, or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. RESULTS: Women without a history of PMS showed cyclicity in both negative mood and physical symptoms while on 400 mg/day progesterone but not on the higher dose or the placebo. Women without a history of PMS had more physical symptoms on progesterone treatment compared with placebo. Women with prior PMS reported no progesterone-induced symptom cyclicity. CONCLUSION: In women without prior PMS natural progesterone caused negative mood effects similar to those induced by synthetic progestogens.

Affect↗

PubMed2003

The role of hormones and hormonal treatments in premenstrual syndrome.

Premenstrual syndrome (PMS) is a menstrual cycle-linked condition with both mental and physical symptoms. Most women of fertile age experience cyclical changes but consider them normal and not requiring treatment. Up to 30% of women feel a need for treatment. The aetiology is still unclear, but sex steroids produced by the corpus luteum of the ovary are thought to be symptom provoking, as the cyclicity disappears in anovulatory cycles when a corpus luteum is not formed. Progestogens and progesterone together with estrogen are able to induce similar symptoms as seen in PMS. Symptom severity is sensitive to the dosage of estrogen. The response systems within the brain known to be involved in PMS symptoms are the serotonin and GABA systems. Progesterone metabolites, especially allopregnanolone, are neuroactive, acting via the GABA system in the brain. Allopregnanolone has similar effects as benzodiazepines, barbiturates and alcohol; all these substances are known to induce adverse mood effects at low dosages in humans and animals. SSRIs and substances inhibiting ovulation, such as gonadotrophin-releasing hormone (GnRH) agonists, have proven to be effective treatments. To avoid adverse effects when high dosages of GnRH agonists are used, add-back hormone replacement therapy is recommended. Spironolactone also has a beneficial effect, although not as much as SSRIs and GnRH agonists.

Clinical Trials as Topic↗