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Biomedical subjects

M Bixo

Publications and source records attributed to M Bixo.

At least 19 recordsLinked to original sources

Long-term effects of two different continuous combined regimens of hormone replacement therapy on well-being.

Our aim was to compare the effect on well-being of two different continuous combined hormone replacement therapies (HRT) in women starting treatment ('starters') and women switching from mainly sequential HRT ('switchers'). The design was a randomized, double-blind, 1-year, prospective study, including 249 postmenopausal women treated with 0.625 mg conjugated estrogen (CE)/5 mg medroxyprogesterone acetate (MPA) or 2 mg estradiol/1 mg norethisterone acetate (NETA) continuously. The main outcome measure was well-being, reported daily on a validated symptom scale during treatment cycles 1, 2, 6 and 13. Both treatment groups, starters and switchers, improved significantly in episodes of sweating during the first 6 months (p < 0.05). Women treated with estradiol/NETA experienced more breast tenderness compared to women using CE/MPA during the whole study period (p < 0.001), whereas there were no differences in negative mood symptoms between treatment groups. Starters experienced improved well-being during the whole study, whereas switchers experienced a transient improvement during the first 2 months. Overall, negative mood symptoms were more frequently reported by women with a history of premenstrual syndrome (PMS) (p < 0.05). Progestogen side-effects were more pronounced with estradiol/NETA than with CE/MPA combinations. Individual factors, such as previous PMS and previous HRT use, should be taken into consideration when prescribing HRT.

Double-Blind Method↗

Well-being at onset of hormone replacement therapy: comparison between two continuous combined regimens.

OBJECTIVES: To compare the effect on well-being of two continuous combined hormone replacement therapies (HRTs) in women starting treatment ('starters') and women switching from mainly sequential HRT ('switchers'). METHODS: This was a randomized, double-blind, 1-month trial, in which 249 postmenopausal women were treated with either conjugated estrogen plus medroxyprogesterone acetate (CE/MPA 0.625 mg/5 mg) or 17beta-estradiol plus norethisterone acetate (E2/NETA 2 mg/1 mg) continuously. Twelve items for measuring climacteric symptoms and well-being were reported daily on a validated symptom scale. RESULTS: Women taking CE/MPA reported lower scores for breast tenderness (p = 0.005), depression (p = 0.019), irritability (p = 0.004) and tension (p = 0.048), compared with women taking E2/NETA. Compared with pretreatment, both groups developed side-effects during the first week: breast tenderness, swelling and depression (p < 0.05). Starters, but also switchers, improved in sweats (p < 0.001 and p = 0.030). Compared with pretreatment ratings, switchers reported higher scores for breast tenderness (p < 0.001), depression (p = 0.050) and negative effects on daily life (p < 0.001), whereas starters reported only physical side-effects (p < 0.05). A history of premenstrual syndrome (PMS) predicted high scores for swelling (p = 0.023), depression (p = 0.024), tension (p = 0.009), irritability (p = 0.027), headache (p < 0.001) and negative effects on daily life (p < 0.001). CONCLUSIONS: CE/MPA 0.625 mg/5 mg is better tolerated than E2/NETA 2 mg/1 mg, and starters react differently from switchers. Side-effects occur more quickly than benefits with HRT, and are more frequent in women with previous PMS.

Breast↗

The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy.

The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate (MPA) during postmenopausal hormone replacement therapy (HRT) in women with and without a history of premenstrual syndrome (PMS). The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden. The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle. The main outcome measures were mood and physical symptoms noted on a daily rating scale. We found that physical symptoms did not differ between 10 and 20 mg MPA. Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA. In women with previous PMS the higher dose of MPA enhanced positive mood symptoms. With respect to mood and physical symptoms, the aim to lower MPA doses in HRT is unwarranted.

Affect↗

Neuroactive steroids and central nervous system disorders.

Steroid hormones are vital for the cell life and affect a number of neuroendocrine and behavioral functions. In contrast to their endocrine actions, certain steroids have been shown to rapidly alter brain excitability and to produce behavioral effects within seconds to minutes. In this article we direct attention to this issue of neuroactive steroids by outlining several aspects of current interest in the field of steroid research. Recent advances in the neurobiology of neuroactive are described along with the impact of advances on drug design for central nervous system (CNS) disorders provoked by neuroactive steriods. The theme was selected in association with the clinical aspects and therapeutical potentials of the neuroactive steroids in CNS disorders. A wide range of topics relating to the neuroactive steroids are outlined, including steroid concentrations in the brain, premenstrual syndrome, estrogen and Alzheimer's disease, side effects of oral contraceptives, mental disorder in menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive steroids in epilepsy treatment.

Alzheimer Disease↗

Binding of [3H]paroxetine to serotonin uptake sites and of [3H]lysergic acid diethylamide to 5-HT2A receptors in platelets from women with premenstrual dysphoric disorder during gonadotropin releasing hormone treatment.

Changes in serotonergic parameters have been reported in psychiatric conditions such as depression but also in the premenstrual dysphoric disorder (PMDD). In addition, hormonal effects on serotonergic activity have been established. In the present study, binding of [3H]paroxetine to platelet serotonin uptake sites and binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors were studied in patients with PMDD treated with a low dose of a gonadotropin releasing hormone (GnRH) agonist (buserelin) or placebo and compared to controls. The PMDD patients were relieved of premenstrual symptoms like depression and irritability during buserelin treatment. The number of [3H]paroxetine binding sites (Bmax) were significantly higher in the follicular phase in untreated PMDD patients compared to controls. When treated with buserelin the difference disappeared. No differences in [3H]LSD binding between the three groups were shown. The present study demonstrated altered platelet [3H]paroxetine binding characteristics in women with PMDD compared to controls. Furthermore, [3H]paroxetine binding was affected by PMDD treatment with a low dose of buserelin. The results are consistent with the hypothesis that changes in serotonergic transmission could be a trait in the premenstrual dysphoric disorder.

Adult↗

Prevalence of psychiatric disorders in gynecologic outpatients.

OBJECTIVE: This study was undertaken to determine the point prevalence of psychiatric disorders in an unselected gynecologic population. STUDY DESIGN: Participants were 1013 consecutive women attending 2 outpatient gynecology clinics in northern Sweden between November 16 and December 15, 1998. The Primary Care Evaluation of Mental Disorders (PRIME-MD) was used as a diagnostic tool for evaluating mood, anxiety, and eating disorders. RESULTS: Overall, 897 patients (88.5%) filled in the diagnostic tool's patient questionnaire. Psychiatric disorders were present in 30.5% of the patients. Mood disorders were most common; major depression was prevalent in 10.1% of patients and minor depression was seen in 12.4% of patients. Anxiety disorders were also common and were encountered in 12.1% of patients. Among patients with a diagnosis, only 21.4% had some form of treatment. CONCLUSIONS: The prevalence of mood and anxiety disorders in an outpatient gynecology clinic is high. The majority of women with a diagnosis based on the diagnostic tool did not have a previous diagnosis and were untreated.

Adolescent↗

Patients with psychiatric disorders in gynecologic practice.

OBJECTIVE: The relationship between different gynecologic complaints and somatic symptoms was studied in a gynecologic population in which the prevalence of psychiatric disorders had been established. STUDY DESIGN: The prevalence of depression and anxiety in the unselected population of 1013 subjects was 27.2% and 12.1%, respectively, as assessed by the Primary Care Evaluation of Mental Disorders (PRIME-MD). The subjects' medical charts were reviewed after the PRIME-MD diagnosis was made. RESULTS: Depression and anxiety disorders were significantly more common among those seeking care for abdominal pain, those who made frequent and unscheduled visits, and those who were hospitalized for acute care. All the physical symptoms indicated in the PRIME-MD Patient Health Questionnaire were more common among women with a psychiatric diagnosis compared with controls. CONCLUSIONS: The majority of cases of depression and anxiety in women are undiagnosed and untreated, and patients with these disorders often present with physical symptoms. Because gynecologic outpatients with abdominal pain, frequent and unscheduled visits, and admissions due to acute illness are more likely to have a psychiatric disorder, it is desirable that gynecologists recognize and treat these problems.

Abdominal Pain↗

Negative mood changes during hormone replacement therapy: a comparison between two progestogens.

OBJECTIVE: The aim of this study was to compare side effects of medroxyprogesterone acetate and norethindrone acetate during postmenopausal hormone replacement therapy in women with and without a history of premenstrual syndrome. STUDY DESIGN: Fifty-one postmenopausal women were randomly selected in a double-blind crossover study. The women received 2 mg of estradiol continuously during five 28-day cycles and 10 mg of medroxyprogesterone or 1 mg of norethindrone sequentially for 12 days of each cycle. Daily symptom rating scales were kept. RESULTS: The women showed cyclic changes, with negative mood and physical symptoms culminating during the late progestogen phase and positive mood during the estrogen-only phase. Symptoms declined with time but remained after 5 months. Women with a history of premenstrual syndrome responded strongly to both progestogens. Medroxyprogesterone acetate induced less negative and more positive mood symptoms than norethindrone in women with no history of premenstrual syndrome. In both groups medroxyprogesterone caused more physical symptoms than norethindrone. CONCLUSION: The addition of medroxyprogesterone to estrogen is preferable to norethindrone with respect to mood symptoms in women without a history of premenstrual syndrome.

Affect↗

Compliance to antidepressant drug therapy for treatment of premenstrual syndrome.

Serotonin reuptake inhibitors (SSRIs) have today become the first-line treatment of premenstrual dysphoric disorder (PMDD). However, the actual success rate of these agents in clinical practice also depends on factors such as adequate dosing, duration of therapy and patient compliance. The aim of the current study was to investigate compliance and reasons for discontinuing tricyclic antidepressant (TCA) or SSRI treatment which had been prescribed for premenstrual syndrome. All women who were given an SSRI or TCA prescription for premenstrual symptoms at three gynecologic practices between January 1994 and December 1997 received a written questionnaire. In all, 202 women received the questionnaire, of whom 84.2% replied. Thirteen per cent never started TCA or SSRI treatment and 54% continued the therapy for more than 6 months. Reasons for discontinuing SSRI or TCA were negative side-effects (43%), other reasons (29%), a wish to deal with the problems 'naturally' (23%), fear of dependence (19%), not wanting to take these drugs (20%) and a desire to find out if the premenstrual symptoms had ended (18%). The main reason for poor compliance was negative side-effects, most often sexual dysfunction. The results of this study suggest that the future challenge in this area for gynecologists will be to ensure adequate education of patients and adequate monitoring of the initial phase of treatment.

Antidepressive Agents, Tricyclic↗

Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen.

BACKGROUND: GnRH agonists constitute a well-documented treatment for premenstrual syndrome (PMS). However, the hypo-estrogenic state induced by the treatment renders it less suitable for long-term clinical use. The aim of the current study was to investigate the efficacy of a low dose GnRH agonist with respect to its ability to relieve premenstrual symptoms and maintain regular ovulatory cycles. METHODS: The effect of a low dose GnRH agonist (buserelin) on luteal phase symptomatology was evaluated in 27 women with severe premenstrual syndrome. The design was doubleblind, placebo-controlled and cross-over. Patients were randomized to either GnRH-agonist intranasally in a dosage of 100 microg once daily for two months or placebo for two months before the cross-over was made. The primary outcome measure consisted of daily symptom ratings for mood and physical symptoms made by the patients throughout the study. Adverse events and hormone concentrations were assessed at visits every second week. RESULTS: Premenstrual irritability and depression were significantly relieved by low dose GnRH agonist. Positive symptoms such as friendliness and cheerfulness were also improved during the premenstrual week. Likewise physical symptoms of swelling and headache displayed a significant improvement during buserelin treatment, whereas breast tenderness scores were unaffected by the treatment. The low dose GnRH agonist treatment regimen induced anovulation in as much as 56% of patients, but these subjects were significantly older than those women who maintained ovulatory cycles throughout the study. CONCLUSION: GnRH treatment significantly reduced premenstrual depression and irritability. However, low dose GnRH therapy is prone to induce anovulation, particularly with increasing age.

Adult↗

Progesterone, 5alpha-pregnane-3,20-dione and 3alpha-hydroxy-5alpha-pregnane-20-one in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of progesterone, 5alpha-pregnane-3,20-dione (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) were measured in 17 brain areas and serum in five fertile and five postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of all three steroids. The highest progesterone levels were noted in the amygdala, cerebellum and hypothalamus and the highest levels of 5alpha-DHP and allopregnanolone were seen in the substantia nigra and basal hypothalamus. Brain concentrations of all three steroids were significantly higher in the fertile women in luteal phase compared to their postmenopausal controls (P < 0.01). In general, the study showed that there is a variation in brain concentrations depending on ovarian steroid production, indicating that the secretion pattern during the menstrual cycle is reflected in the brain. However, regional differences in brain steroid levels imply local mechanisms for steroid uptake and binding as well. Investigations of gonadal steroid distributions in the human brain might be of importance considering the actions of these steroids in the central nervous system. Such studies could provide information about physiological mechanisms, such as the ovulation, and also form a baseline for comparative studies of normal and pathological conditions involving steroids, for instance, catamenial epilepsy and the premenstrual tension syndrome.

5-alpha-Dihydroprogesterone↗

Estradiol and testosterone in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of estradiol and testosterone were measured in 17 brain areas, serum and fat in 6 fertile and 5 postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of both steroids. The highest levels of estradiol and testosterone were noted in the hypothalamus, preoptic area and substantia nigra. These findings may assist in the interpretation of functional animal studies where the hypothalamus-preoptic area and the nigrostriatal dopamine system have proved to be target areas for estradiol. When compared to postmenopausal women, estradiol concentrations were significantly higher in the brains of fertile women, which indicates that peripheral serum levels of estradiol are reflected in the brain. This study has yielded information about steroid levels in different endocrine states and could provide a frame of reference for studies of estradiol and testosterone mediated effects on the central nervous system.

Adipose Tissue↗

Sex steroids in human brain tumors and breast cancer.

The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor and breast cancer tissues. The concentrations in malignant gliomas and breast cancers showed interindividual variations, especially evident with regard to estradiol. High estradiol concentrations were recorded in two patients with malignant astrocytoma. The concentrations of 1.00 pg/mg and 3.32 pg/mg were 10 to 30 times as high as in normal female brain. In five of ten astrocytomas the estradiol concentration was higher than the lowest breast cancer value. The distribution of progesterone seemed more even, and the level was significantly lower in brain tumors and breast cancers as compared with female brain, perhaps indicating an increased metabolism. Testosterone levels were somewhat higher in brain tumors, as compared with breast cancers, but not different from values in brain tissue. There were no significant age or sex correlation or differences in the concentrations of steroids in the brain tumors. The results suggest that manipulation of sex steroid metabolism in malignant brain tumors can be of beneficial therapeutic value as has been shown for breast cancer and prostatic carcinoma.

Adolescent↗

Regional distribution of progesterone and 5 alpha-pregnane-3,20-dione in rat brain during progesterone-induced "anesthesia".

Progesterone and 5 alpha-pregnane-3,20-dione (5 alpha-DHP) concentrations were measured in seven brain areas and in plasma during "anesthesia" induced by progesterone (1-2 mg IV) in female rats. The highest levels of progesterone were detected in the striatum and hypothalamus (23.3 +/- 5.27 and 22.7 +/- 4.30 micrograms/g +/- SEM, respectively); these concentrations were approximately 1000 times higher than those during the post-ovulatory phase. Highest levels of 5 alpha-DHP were detected in the striatum and hippocampus (11.5 +/- 1.74 and 10.4 +/- 3.15 micrograms/g +/- SEM, respectively). The ratio of 5 alpha-DHP to progesterone was approximately 100 times higher in brain tissue than in plasma. We conclude that a conversion of progesterone to 5 alpha-DHP occurs in the brain during the course of progesterone-induced "anesthesia". This metabolic step may be an important contributory factor to the anesthetic potency of progesterone.

5-alpha-Dihydroprogesterone↗

Post-mortem stability of progesterone in rat brain.

Progesterone concentrations in the brains of female rats kept at +20 degrees C or +4 degrees C for 0 to 48 hours after death were investigated. After two hours at +20 degrees C the progesterone concentration in seven studied brain areas were equal to that in control brains (dissected immediately after death). After four hours at +20 degrees C, levels decreased significantly in three brain regions. Intact rats that were placed in a refrigerator (+4 degrees C) after four hours at room temperature (+20 degrees C) showed no further changes in brain progesterone concentration. In the control group, the cerebral cortex, the hypothalamus and the hippocampus contained progesterone levels significantly higher than in all other areas (p less than 0.05). After four hours at room temperature only the hypothalamus showed higher levels (p less than 0.05). In conclusion, time after death and storage temperature affect the post-mortem levels of progesterone. Because of their differences in body masses, the conditions in the rat brain are not comparable to those in the human brain. However, it might be possible to study the regional distribution of progesterone in the human brain if control cases matched with regard to post-mortal time and brain temperature are used.

Animals↗

Comparison between pre- and postovulatory distributions of oestradiol and progesterone in the brain of the PMSG-treated rat.

The pre- and postovulatory levels of oestradiol and progesterone were measured in seven brain areas, peripheral fat, muscle tissue and blood plasma in 49 immature female rats which had been given an injection of 4 IU PMSG (Pregnant Mare Serum Gonadotropin) on the 25th day of life. We observed a uniform decline in oestradiol concentration in all the areas of the postovulatory rat. The highest mean concentrations of oestradiol pre- and postovulatory were found in the hypothalamus and the striatum (260 +/- 26, 110 +/- 11, 200 +/- 39 and 75 +/- 13 pg g-1, respectively). The levels of progesterone showed variable increases in all the areas postovulatory. The highest postovulatory concentration was found in the cerebral cortex (29 +/- 2.0 ng g-1) where the increase was six-fold greater than the increases in any of the other areas compared to preovulatory values. The hypothalamus contained high progesterone levels at both times (3.5 +/- 0.68 ng g-1 and 27 +/- 5.2 ng g-1) compared to other areas. We conclude that the female rat brain exhibits differences in the distribution of oestradiol and progesterone both pre- and postovulatory. Since the levels in different brain areas to a large extent varied independently we suggest different uptake mechanisms and/or different binding capacities in various regions of the rat brain.

Animals↗