Biomedical subjects

T Bäckström

Publications and source records attributed to T Bäckström.

At least 19 recordsLinked to original sources

PubMed2006

Oral progesterone decreases saccadic eye velocity and increases sedation in women.

The aim of this study was to investigate the neurophysiological and behavioural effects of a single dose of progesterone in women. Allopregnanolone is a metabolite of progesterone and a potent positive modulator of the GABA(A) receptor and produces sedative and anxiolytic effects. This study was designed to examine the effect of oral progesterone and the metabolite allopregnanolone in women. Women (n=15) in their follicular phase received oral progesterone (400mg) or placebo. Dependent measures included plasma levels of progesterone and allopregnanolone, saccadic eye velocity (SEV), subjective ratings (visual analogue scales), and reaction time. Administration of progesterone decreased SEV and increased sedation. This effect is probably due to enhanced GABA activity.

Absorption↗

PubMed2006

Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor.

The neurosteroid allopregnanolone (ALLO) or 3alpha-OH-5alpha-pregnane-20-one interacts with the GABA type A receptor chloride ion channel complex and enhances the effect of GABA. Animal and human studies suggest that ALLO plays an important role in several disorders including premenstrual syndrome, anxiety, and memory impairment. In contrast to ALLO, steroids with a hydroxy group in the 3beta position usually exert a reducing effect and have recently attracted interest due to their suggested role in counteracting the negative action of ALLO. In this study, five different 3beta-steroids were tested for their ability to modulate GABA-mediated chloride ion uptake in the absence and presence of ALLO in rat brain microsacs preparations. In addition, the effects of the 3beta-steroids and their interaction with ALLO were investigated by patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) in rat hypothalamic neurons from the medial preoptic nucleus (MPN). All tested 3beta-steroids reduced the ALLO-enhanced GABA response in cerebral cortex, in hippocampus and in MPN. In cerebellum, only one had this effect. However, in the absence of ALLO, two of the 3beta-steroids potentiated GABA-evoked chloride ion uptake and prolonged the sIPSCs decay time, whereas the others had little or no effect. Therefore, it is possible that at least some 3beta-steroids can act as positive GABA(A) receptor modulators as well as negative modulators depending on whether or not ALLO is present. Finally, these results suggest that the 3beta-steroids could be of interest as pharmacological agents that could counteract the negative effects of ALLO.

Analysis of Variance↗

PubMed2006

Tolerance development to Morris water maze test impairments induced by acute allopregnanolone.

The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.

Analysis of Variance↗

PubMed2006

Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone.

OBJECTIVES: To investigate the pharmacokinetics of progesterone, allopregnanolone and pregnanolone after treatment with a low oral dose of progesterone. METHODS: Eight postmenopausal women were given a single oral dose of 20 mg of micronised progesterone on Day 1 and 20 mg twice daily on Days 2-7. Blood samples for the analysis of progesterone, allopregnanolone and pregnanolone were collected, and pharmacokinetic parameters were calculated. RESULTS: After ingestion of a single dose, areas under the plasma concentration-time curve (AUC) from 0 to 12 h for progesterone, allopregnanolone and pregnanolone were 127%, 196% and 119% higher than the corresponding AUCs estimated to be caused by endogenous production. The maximum plasma concentration (Cmax) and the AUC values were significantly lower for pregnanolone than for progesterone and allopregnanolone. The trough concentrations at steady state (Css) were significantly higher than the baseline values, and Css for pregnanolone was significantly lower than for allopregnanolone and progesterone. Css for allopregnanolone was in the range of what is normally seen in the menstrual cycle. CONCLUSIONS: After ingestion of a low-dose of progesterone, the concentrations of allopregnanolone were in the same range as those of progesterone. Oral doses of 20 mg of progesterone twice daily to postmenopausal women produced allopregnanolone concentrations comparable to those achieved physiologically in premenopausal women. Low-dose oral progesterone may be used as a prodrug to allopregnanolone when the aim is to investigate low-dose allopregnanolone effects in humans.

Administration, Oral↗

PubMed2006

Adverse mood effects during postmenopausal hormone treatment in relation to personality traits.

OBJECTIVE: When postmenopausal women are treated with sequential hormone therapy (HT), cyclical mood swings similar to symptoms seen in the premenstrual dysphoric disorder (PMDD) are described. Women with a history of premenstrual symptoms (PMS) seem to respond differently to the addition of a progestin to estrogen than women without previous PMS. This study aimed to investigate personality traits and daily mood symptoms in women with a history of PMS and women without, while treated with estrogen and sequential progestin. METHODS: A total of 106 women, who participated in clinical trials designed to evaluate mood and physical responses to sequential estrogen and progestin therapy, filled out the Karolinska Personality Scale (KSP) form, before entering the studies. The treatment consisted of 2 mg estradiol valerate continuously, with an addition of 10 mg medroxyprogesterone acetate (MPA) during the last 12 days of the 28-day cycle. Subjects kept daily symptom ratings using a validated symptom scale during these two treatment cycles, and these were used for the analyses. The study-groups were stratified for a history of PMS or not, appearance of progestin-induced adverse mood effects or not, and symptom cyclicity or not. RESULTS: There was a significant co-variation between the women who reported the highest negative mood scores during the addition of progestin to estrogen and a history of PMS. Women with PMS history reported different personality characteristics as having higher scores of anxiety symptoms of muscular tension, feeling more indirect aggression and lack of impulse control, and being less satisfied with their lives or childhood, compared to women without a PMS history. Women who reported the most intense negative mood symptoms during the progestin phase reported more somatic anxiety, an aim to avoid monotony, a lower satisfaction with life or childhood, and higher scores of indirect aggression and irritability. CONCLUSIONS: Women with a history of PMS and women with a high anxiety-related personality might respond with adverse mood effects to a combination of estrogen and sequential progestin and therefore a thorough evaluation should be made, at the consultation for hormone therapy, of mood benefits or disadvantages before initiation of treatment and there should be a close follow-up after.

Affect↗

PubMed2006

GABA-site antagonism and pentobarbital actions do not depend on the alpha-subunit type in the recombinant rat GABA receptor.

AIM: The roles of alpha-subunits on the gamma-aminobutyric acid (GABA)-site antagonism and pentobarbital actions were examined in rat recombinant GABA(A) receptors in Xenopus oocytes. METHODS: Experiments were performed with binary and ternary GABA(A) receptors containing alpha1-, alpha4- or alpha5-subunit by the two-electrode voltage-clamp technique. RESULTS: The potency of GABA was significantly higher in the alpha1beta2, alpha4beta2 and alpha5beta2 receptors compared with the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. However, the alpha5beta2 receptor possessed significantly lower GABA efficacy compared with the alpha5beta2gamma2L receptor. While the gamma2-subunit was essential to the potency of GABA, its influence on the apparent GABA-site antagonism was less profound. The antagonist affinity constants (K(B)) of bicuculline inhibition and slopes of Schild plots were similar between all types of ternary and binary receptors except alpha5beta2 receptor which was not tested. The pK(B)s and IC(50)s of the GABA-site antagonism were not significantly different between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. Bicuculline blocked pentobarbital-activated currents in a reversible and non-competitive manner with the alpha1beta2gamma2L, alpha4beta2gamma2L, and alpha5beta2gamma2L receptors, indicating an allosteric inhibition of the GABA-site. No significant difference of bicuculline potencies in inhibiting GABA- and pentobarbital-activated currents was found between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. CONCLUSION: The GABA-site antagonism does not depend on the subtype of alpha-subunits. Similarly, pentobarbital activates ternary receptors composed of different alpha-subunits in a bicuculline-sensitive manner. The potencies of bicuculline to inhibit pentobarbital-activated currents are identical with receptors containing alpha1, alpha4 or alpha5-subunit. The alpha1beta2 and alpha4beta2 receptors possess higher GABA potencies compared with the alpha1beta2gamma2L and alpha4beta2gamma2L receptors.

Animals↗

PubMed2005

Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor.

Glucocorticoids and neurosteroids, such as allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress. A non-genomic effect of glucocorticoids has been established but is not yet fully understood. We have studied the effect of glucocorticoid metabolites on the gamma-aminobutyric acid (GABA) system. In these experiments we studied the effects of the glucocorticoid metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone and tetrahydrocortisone in rat cortical microsacs. Our results showed that both these cortisol and cortisone metabolites reduce GABA-mediated chloride ion uptake. This reduction was not observed in the presence of allopregnanolone but allotetrahydrocortisol interacts with allopregnanolone, enhancing the allopregnanolone-stimulated potentiation of GABA-mediated chloride ion uptake. This enhanced effect was completely blocked by the addition of 30 microm of the 3beta-isomer of allopregnanolone, isoallopregnanolone. Our findings show that steroids released during stress interact with each other and GABA in the GABA system.

Animals↗

PubMed2004

Dynamic aspects of acute tolerance to allopregnanolone evaluated using anaesthesia threshold in male rats.

BACKGROUND: It is unclear if allopregnanolone (AlloP) anaesthesia can induce tolerance. Acute tolerance is defined as altered sensitivity to a drug during a single continuous exposure. METHODS: Induction of acute tolerance to AlloP was studied in male rats using a threshold technique of deep anaesthesia. AlloP was infused at a dose rate of 4.0 mg kg(-1) min(-1). The infusion was stopped when a burst suppression of 1 s or more (the "silent second", SS) occurred in the EEG. To maintain anaesthesia, the infusion was restarted when no SS had been seen in the EEG for 1 min. This interrupted targeted infusion towards an EEG end-point (SS) was continued until 30, 60 or 90 min of anaesthesia had been reached. At these times the rats were killed and AlloP concentrations in serum, muscle, fat and different brain regions were determined by radioimmunoassay. RESULTS: Maintenance dose rate (MDR) was calculated using 20-min intervals. During anaesthesia the MDR increased (P<0.001) from 0.67 (sem 0.03) mg kg(-1) min(-1) (in the interval 10-30 min) to 0.98 (0.04) mg kg(-1) min(-1) (in the interval 65-85 min). After 60 min a slight increase in MDR was observed. After 90 min of anaesthesia the AlloP concentrations in the hippocampus and brainstem had increased by more than 50% compared with control values of 25.2 (1.13) and 52.7 (5.81) nmol g(-1) respectively, and after 60 min to around 40%. At 30 min no increase was seen in any brain region analysed. CONCLUSIONS: Measurements in vivo and in vitro record acute tolerance to AlloP occurring with a delay.

Adipose Tissue↗

PubMed2004

Intratumoral effects of medroxy-progesterone on proliferation, apoptosis, and sex steroid receptors in endometrioid endometrial adenocarcinoma.

OBJECTIVE: The effects of progesterone on proliferation and apoptosis are studied in a scrutinized evaluation of endometrial carcinoma before, during, and after progesterone therapy. The heterogeneity of sex steroid expression as well as proliferation, indicated as Ki-67 index, is considered. METHODS: A total of 29 endometrial carcinomas were studied with in situ evaluation of Ki-67 proliferation marker, estrogen and progesterone receptors (ER and PR), and bcl-2 and p53 immunohistochemistry in the epithelial part of the tumor. In biopsy 1, before the therapy, Ki-67 ER, and PR were studied also in stroma. Apoptotic cells were morphologically identified in hematoxylin- and eosin-stained sections of the tumors and the apoptotic index (apoptotic cells per 1000 cells) was calculated. Chances in feature factors were mainly evaluated by repeated measures ANOVA. RESULTS: Proliferation (Ki-67) was decreased in grade 1 (G1) and grade 2 (G2) tumors during progesterone therapy both in overall evaluation (Ki) and particularly in the areas of maximal proliferation (Ki-max). No change was seen in G3 tumors. A decrease in PR expression in the areas of maximal expression for PR (PR-max) was also observed in G1 and G2 tumors. Apoptosis as well as bcl-2 and ER expression were unchanged during therapy and withdrawal. CONCLUSIONS: The effect of progesterone is seen only on proliferation in low-grade (G1 and G2) tumors. The coexistence of high PR expression in the foci of high proliferation may contribute to the effect in G1 and G2 tumors. No effect of progesterone is seen on apoptosis in tumors of any grade.

Adenocarcinoma↗

PubMed2004

Intravasal microdialysis is superior to intramyocardial microdialysis in detecting local ischaemia in experimental porcine myocardial infarction.

OBJECTIVE: A novel application of microdialysis was studied, where myocardial outflow of energy metabolites was monitored by intravasal microdialysis in the myocardial venous outflow during ischaemia and reperfusion. These levels where related to levels monitored by microdialysis catheters placed intramyocardially. METHODS: Microdialysis catheters were introduced into the great cardiac vein (GCV), ischaemic myocardium and non-ischaemic myocardium in 10 anaesthetized pigs. The left anterior descending coronary artery was occluded for 60 min in five pigs and five pigs served as controls. Ischaemia was followed by 120 min of reperfusion. Microdialysis samples were analysed for glucose, lactate, pyruvate and glycerol. Venous lactate and glucose levels were measured by blood samples from the femoral vein. RESULTS: All animals subjected to ischaemia developed myocardial infarction. Lactate, lactate/pyruvate ratio and glycerol increased in the microdialysis samples from the GCV and the catheter placed in ischaemic myocardium while no changes were detected in samples from the catheter placed in the non-ischaemic myocardium. CONCLUSION: In this study, we have demonstrated that intravasal microdialysis catheters rapidly and reliably detect local myocardial ischaemia, while intramyocardially placed microdialysis catheters will not show these changes if placed in a non-ischaemic area.

Animals↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2003

Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden.

OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.

Abortion, Spontaneous↗

PubMed2003

The influence of premenstrual symptoms on postural balance and kinesthesia during the menstrual cycle.

Recent studies have indicated an increased incidence of female athletic injuries during the luteal phase and the first days of the menstrual period. The purpose of this study was to investigate whether postural sway and knee-joint kinesthesia very during the menstrual cycle, and whether premenstrual syndrome (PMS) influences postural balance and kinesthesia. A total of 13 subjects with regular menstrual cycles participated in the study. Postural sway and kinesthesia were measured in the early follicular phase, in the ovulation phase and in the mid-luteal phase. Postural sway was measured with an ankle disc placed on a Statometer, and kinesthesia was measured with a specially designed device. Menstrual cycle phases were determined by sex hormone analyses in serum and by luteinizing hormone (LH) detection in urine. The diagnosis of PMS was made prospectively using validated daily symptom ratings. Eight of 13 women were classified as having PMS. These women had a significantly greater postural sway (p = 0.002) and a greater threshold for detection of passive motion in the knee joints (p = 0.05) than women without PMS. A tendency (p = 0.06) towards greater postural sway in the mid-luteal phase was detected among women with PMS. This may explain the finding of an increased incidence of athletic injuries in the luteal phase, reported previously.

Adult↗

PubMed2003

Apoptosis, proliferation, and hormone receptors in endometrial carcinoma: results depending on methods of analysis.

Apoptosis and proliferation were studied in 29 endometrial adenocarcinomas of the endometrioid type and characterized by the immunohisto-chemical pattern of estrogen receptor (ER) alpha and progesterone receptor (PR) expression. Intratumoral heterogeneous distribution of both ER and PR as well as of the proliferation marker Ki-67 was studied and quantified. Both density and heterogeneity of the two steroid receptors and Ki-67 varied, depending on the histological malignancy grade (grades 1-3, or G1-3); interestingly, however, the apoptotic index (Ai) was in the same range for all grades. Receptor staining was evaluated by three different methods: i) counting the percentage of stained cells (staining index), according to stereological principles; ii) the mixed method, a combination of the staining index results and ranking staining intensity; and iii) a superficial and rapid visual scoring. The three methods gave equal results. Apoptotic cells and bodies were generally scattered in the endometrial carcinoma but more frequently observed adjacent to necrotic foci. Bcl-2, known as anti-apoptotic factor, showed no correlation to apoptotic index, Ki-67 expression, ER, or PR. Overexpression of p53 was seen in two tumors of grade 3. In a detailed study of intra-tumoral microfoci performed on consecutively taken tissue sections, a higher staining index of both ER and PR was found in the areas of maximal proliferation compared with the areas of minimal proliferation in tumors of grades 1-2, but not in G3 tumors. Other covariations were also found when non-specified areas were studied. The Ki-67 index was both higher and more heterogeneous in G2-3 tumors than in G1 tumors. Our results indicate that there is an increasing discrepancy between cell death and cell proliferation with progressing tumor grade, which may contribute to the differences in tumor aggressivity.

Apoptosis↗

PubMed2003

Effects of sex steroids on survival and receptor expression in ovarian epithelial tumour cells.

The factors that govern the genesis and progression of ovarian cancer remain unclear. It is thought that ovarian tumours are endocrine related and hormone dependent. We therefore investigated the effects of the sex steroids progesterone, testosterone and 17 beta-estradiol on tumour cell survival and the expression of estrogen receptors (ER) and progesterone receptors (PR) in tumour cells. The study was performed on primary cell cultures derived from patients suffering from epithelial ovarian cancer. The majority of the cells isolated expressed ER and PR to some degree, the combination ER+/PR+ was the most common. Both ER and PR expression decreased after 72-h culture, revealing an unexpectedly dynamic system. The survival rates of cells cultured in progesterone seemed to be inversely related to their PR expression. Lowering levels of 17 beta-estradiol and testosterone in cell cultures reduced cell survival, but it appears that this observation depends on factors other than ER.

Adult↗

PubMed2002

Atypical attack of acute intermittent porphyria--paresis but no abdominal pain.

We report a case of acute intermittent porphyria (AIP) in a 45-year-old woman. Her first attack occurred at the age of 38. Because of escalating cyclical premenstrual attacks, the following 2 years, depletion of the endogenous sex hormone was considered as haeme arginate treatment proved insufficient. Gonadotropin releasing hormone agonist treatment with low-dose oestradiol add back was quite successful initially but was abandoned after 18 months when progesterone add back precipitated a severe attack. Following hysterectomy and oophorectomy at age 42 and oestradiol add back, a remarkable monthly regularity of attacks ensured periodically but with milder symptoms. Two years after surgery, preceded by six attack-free months, a puzzling symptom-shift occurred, from abdominal pain, back and thigh pain during the attacks, to solely severe distal extensor paresis in the arms. Haeme arginate treatment interrupted the progress of the paresis almost immediately and motor function improved considerably up to the 9-month follow-up. Electrophysiological examination revealed only motor neuropathy, consistent with axonal degeneration. Subsequently the symptoms changed yet again, to sensory disturbances with numbness and dysesthesia as the primary expression followed by rather mild abdominal pain. However, cyclical attacks occurred, despite absence of endogenous ovarial hormone production, possibly attributable to impaired oestrogen metabolism in the liver, or adrenal oestrogen production. Treatment comprising oophorectomy, low-dose oestradiol add back and haeme arginate infusion for 2 days on the appearance of early AIP symptoms is now quite successful affording improvement in life quality.

Abdominal Pain↗

PubMed2002

Low sex steroid environment affects survival and steroid secretion of ovarian tumour cells in primary cultures.

Ovarian epithelial tumours are considered to be endocrine related. The effects of an environment with low levels of the steroid hormones 17 beta-estradiol, testosterone or progesterone on cell survival and steroid secretion were studied in primary cell cultures derived from 25 patients suffering from epithelial ovarian tumours. Tumour cells cultured in 17 beta-estradiol and testosterone showed a reduced cell survival (-10.3 +/- 2.3% and -15.6 +/- 2.7% minimum survival respectively). This reduction was inversely proportional to hormone concentrations within the range studied. No similar effect was observed in the progesterone cultures. It was found that 17 beta-estradiol was secreted from the primary cell cultures and, interestingly, the amount of 17 beta-estradiol secreted increased with increasing levels of 17 beta-estradiol in the environment. Neither progesterone nor testosterone production was observed in any of the cultures studied. It is believed that 17 beta-estradiol has an antiapoptotic effect on ovarian surface epithelial (OSE) cells. Reduction of 17 beta-estradiol in the environment may inhibit this effect, resulting in reduced cell survival. The ability of ovarian epithelial tumour cells to secrete 17 beta-estradiol suggests that epithelial ovarian tumours play an active role in altering their own hormonal environment, promoting tumour progression.

Adult↗