Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls-a pilot study.

Rationale: In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABAA receptor, enhancing the effect of γ-aminobutyric acid (GABA).

Women with polycystic ovary syndrome have elevated serum concentrations of and altered GABA(A) receptor sensitivity to allopregnanolone.

Objective: Several studies have reported that γ-aminobutyric acid (GABA) ergic circuits are involved in the pathophysiology of polycystic ovary syndrome (PCOS). The progesterone metabolite allopregnanolone is a potent GABA(A) -receptor-modulating steroid, and patients may have increased concentrations of allopregnanolone or altered GABAA receptor sensitivity. We investigated both of these possibilities in this study.

Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans.

Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of γ-amino-butyric acid (GABA) on the GABA type A (GABAA) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity.

Erratum to: Women with PTSD have a changed sensitivity to GABA-A receptor active substances.

Erratum to: Pyschopharmacology, DOI 10.1007/s00213-014-3776-y . In the original publication of this paper the name of the first author was incorrectly rendered as “Möller AT.

Women with PTSD have a changed sensitivity to GABA-A receptor active substances.

Rationale: The use of benzodiazepines in treating anxiety symptoms in patients with posttraumatic stress disorder (PTSD) has been debated. Studies on other anxiety disorders have indicated changed sensitivity to GABA-A receptor active substances.

Objective: In the present study, we investigated the GABA receptor sensitivity in PTSD patients.

Posttraumatic stress among women after induced abortion: a Swedish multi-centre cohort study.

Background: Induced abortion is a common medical intervention. Whether psychological sequelae might follow induced abortion has long been a subject of concern among researchers and little is known about the relationship between posttraumatic stress disorder (PTSD) and induced abortion. Thus, the aim of the study was to assess the prevalence of PTSD and posttraumatic stress symptoms (PTSS) before and at three and six months after induced abortion, and to describe the characteristics of the women who developed PTSD or PTSS after the abortion.

The prevalence of posttraumatic stress among women requesting induced abortion.

Objectives: To describe the prevalence and pattern of traumatic experiences, to assess the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS), to identify risk factors for PTSD and PTSS, and to analyse the association of PTSD and PTSS with concomitant anxiety and depressive symptoms in women requesting induced abortion.

Methods: A Swedish multi-centre study of women requesting an induced abortion. The Screen Questionnaire - Posttraumatic Stress Disorder was used for research diagnoses of PTSD and PTSS.

Allopregnanolone serum concentrations and diurnal cortisol secretion in women with premenstrual dysphoric disorder.

Most prior studies in patients with premenstrual dysphoric disorder (PMDD) indicate a blunted hypothalamus-pituitary-adrenal axis function. However, the relationship between neuroactive progesterone metabolites, such as allopregnanolone, and hypothalamus-pituitary-adrenal (HPA) axis function in PMDD patients is relatively sparsely studied. The primary aims of this study were to assess diurnal variation in circulating cortisol and low-dose dexamethasone suppression in PMDD patients and healthy controls, and the relationship between these two HPA axis indices and allopregnanolone serum concentrations.

Increased neurosteroid sensitivity--an explanation to symptoms associated with chronic work related stress in women?

Work related psychosocial stress can be accompanied by so called burnout syndrome with symptoms of mental exhaustion, physical fatigue, and cognitive dysfunction. Underlying mechanisms for acquiring burnout syndrome are not clear. Animal studies show that chronic stress is associated with altered release of GABA-A receptor modulating steroids (GAMS), altered composition of the GABA-A receptor and altered sensitivity to GAMS.

Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol.

Background: The purpose of this study was to investigate how women without and with different severity of premenstrual symptoms react to treatment with a combined oral contraceptive containing 250-mcg norgestimate/35-mcg ethinyl estradiol (EE). Focus was placed on mood and physical symptoms.

Study Design: This open, prospective study evaluated 24 women using norgestimate/EE for three cycles in a 21/7 regimen.

How to determine symptom severity in premenstrual syndrome: a combination of daily symptom ratings and interviews.

Objective: To investigate how premenstrual symptoms are experienced and affect daily life, and to see if there is an agreement in reported symptom severity based on interviews compared to ratings on a symptom rating scale.

Study Design: Twenty-two women with different degree of premenstrual symptoms were interviewed about their symptoms. Based on the luteal-phase interviews, they were categorized in four different severity groups: severe (n=5), moderate (n=3), mild (n=8), and no symptoms/cyclicity (n=6).

Prevalence of violence exposure in women with premenstrual dysphoric disorder in comparison with other gynecological patients and asymptomatic controls.

Objective: The aim of the present study was to estimate prevalence rates of physical, emotional and sexual abuse in women with premenstrual dysphoric disorder (PMDD) in comparison with gynecological outpatients and asymptomatic healthy control subjects.

Design: Cross-sectional study.

Settings: Departments of obstetrics and gynecology in three different Swedish hospitals.

Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.

Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABA(A)) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABA(A) receptor effects.

Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder.

Objective: The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy.

Study Design: Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.

Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators.

Unlabelled: Certain women experience negative mood symptoms as a result of progesterone during the luteal phase of the menstrual cycle, progestagens in hormonal contraceptives, or the addition of progesterone or progestagens in sequential hormone therapy (HT). This phenomenon is believed to be mediated via the action of the progesterone metabolites on the GABA(A) system, which is the major inhibitory system in the mammalian CNS. The positive modulators of the GABA(A) receptor include allopregnanolone and pregnanolone, both neuroactive metabolites of progesterone, as well as benzodiazepines, barbiturates, and alcohol.

Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women.

Rationale: The pharmacokinetics and behavioral effects of isoallopregnanolone (3beta-hydoxy-5alpha-pregnan-20-one) in women are not known.

Objectives: Allopregnanolone (3alpha-hydoxy-5alpha-pregnan-20-one) is a well-known neurosteroid, acting via the GABA(A) receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3beta-stereoisomer of allopregnanolone.

Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone therapy.

Background: We have previously compared the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during sequential treatment with estradiol-only (E2-only) and estradiol together with progesterone (E2 + P) in postmenopausal women. The aim of the present study was to evaluate the pharmacodynamic response to pregnanolone during withdrawal from E2-only treatment and during withdrawal from treatment with E2 + P.

Method: Twenty-six postmenopausal women were administered hormone therapy (HT) in a randomized, double blinded, placebo-controlled, crossover study.

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.

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.

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.

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.

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.

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.

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.