Progesterone increases the number of Langerhans cells in human vaginal epithelium.
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Publications and source records attributed to J C Huber.
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OBJECTIVE: Proinflammatory cytokines have been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism in exon 5 of the interleukin-1beta gene (IL1B) and interleukin-1beta (IL-1beta) serum levels. DESIGN: Case control study. SETTING: Academic research institution. SUBJECTS: One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 68 healthy controls with at least two live births and no history of pregnancy loss. INTERVENTIONS: Peripheral venous puncture. MAIN OUTCOME MEASURES: An IL1B exon 5 (position +3953) gene polymorphism was analyzed by PCR amplification followed by restriction fragment length polymorphism analysis. IL-1beta serum levels were analyzed by a commercially available ELISA. RESULTS: Allele frequencies in women with IRM and controls were 77.9% and 80.8%, respectively, for the E1 allele (wild type), and 22.1% and 19.2%, respectively, for the E2 allele (mutant). No association between the E2 allele and the occurrence of IRM was found (P=.57, odds ratio =.83). Genotype frequencies and IL-1beta serum levels were not significantly different between the study group and the control group. CONCLUSIONS: This is the first report on an IL1B polymorphism in IRM. Although known to alter IL-1beta expression, the investigated IL1B polymorphism is not associated with IRM and increased serum levels in a large Caucasian population.
OBJECTIVE: To investigate the frequency of a polymorphism in intron 7 of the tryptophan hydroxylase gene among women with idiopathic recurrent miscarriage and healthy controls. METHODS: In a case control study, we studied 125 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 137 healthy controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the A218C polymorphism in intron 7 of the tryptophan hydroxylase gene. RESULTS: Allele frequencies among women with idiopathic recurrent miscarriage and controls were 32.4% and 38.7%, respectively, for allele A (wild type) and 67.6% and 61.3%, respectively, for allele C (mutant). No association between the presence of allele C and idiopathic recurrent miscarriage was found (P = .3; odds ratio 1.31; 95% confidence interval 0.93, 1.87). Genotype frequencies also were not significantly different between the study group (C/C: 44.8%; A/C: 45.6%; A/A: 9.6%) and the control group (C/C: 37.2%; A/C: 48.2%; A/A: 14.6%; P = .2). Between women with primary and women with secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed (63% vs 62% for allele C and 31% vs 38% for allele A; P = .3). CONCLUSION: The A218C polymorphism in intron 7 of the tryptophan hydroxylase gene is not associated with idiopathic recurrent miscarriage.
OBJECTIVE: To perform an observational study of the demographics, clinical factors, and therapeutic efficacy in patients presenting to the emergency department with a chief complaint of headache. BACKGROUND: Acute headache presentations to the emergency department are a therapeutic dilemma for physicians. METHODS: Patients presenting with nontraumatic headache to the emergency department of Hermann Hospital in Houston, Texas, during a 16-month period were prospectively ascertained by active and passive surveillance. The medical record was abstracted. Demographic and clinical information are presented with descriptive statistics. Relative benefit of individual therapies are compared with odds ratios (95% confidence intervals). RESULTS: Of the 38 730 patients who were prospectively screened, 455 presented with a chief complaint of headache. Seventy-six percent were women, and the mean age was 37 years. Non-Hispanic whites were more likely diagnosed with migraine compared with Hispanics or African Americans (P<.001). Three percent had subarachnoid hemorrhage. Neurologist follow-up was ordered in 10%. The median time in the emergency department was 265 minutes. With the initial treatment, 44% resolved, 47% improved, and 9% had no change; none worsened. In comparison with all other therapies used, there was a trend suggesting the superiority of antiemetics (odds ratio, 2.66; 95% confidence interval, 0.81 to 8.61). Acetaminophen was less helpful (odds ratio, 0.27; 95% confidence interval, 0.10 to 0.70). When comparing specific agents to therapies which could be used at home, antiemetics led to headache resolution most often (odds ratio, 3.18; 95% confidence interval, 1.40 to 7.22); ketorolac showed a similar trend (odds ratio, 2.05; 95% confidence interval, 0.86 to 4.89). CONCLUSIONS: Headache in the emergency department is a phenomena of young women who spend a long time waiting and receive many tests. A variety of therapies are used. Antiemetics may be especially useful for headache resolution.
AIM: The aim of this study was to show the influence of three different hormone replacement therapy regimes (HRT) by comparing the changes in skin thickness. METHOD: Skin thickness was measured using a high-frequency ultrasound system on the inner side of the left upper arm of perimenopausal women with a low oestradiol level (< 45 pg/ml). The patients were allocated to different groups: Group1 (n = 6) received oestradiol merely transdermally; Group 2 (n = 7) was given transdermal oestradiol as well as progesterone vaginally; Group 3 (n = 8) took oral oestradiol and vaginal progesterone; Group 4 (n = 3) served as the control group without therapy. RESULTS: The median value of skin thickness in all HRT-groups increased highly significantly (0.15 mm) after six months (0.91 mm before therapy versus 1.06 mm after six months of HRT), but there was no significant change in the control group. CONCLUSIONS: The study shows that HRT leads to an increase of skin thickness which can be demonstrated by a high-frequency ultrasound.
BACKGROUND: Lack of endothelium-derived nitric oxide is associated with vasospasm and vascular infarction. We investigated the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding endothelial nitric oxide synthase (NOS3). METHOD: In a prospective case-control study, 105 women with idiopathic recurrent miscarriage and 91 healthy controls were investigated. We used the polymerase chain reaction to identify the different alleles of a 27 base pair tandem repeat polymorphism in intron 4 of the NOS3 gene. RESULTS: The wild type B allele was identified on 329 out of 392 chromosomes (frequency 0.84). The polymorphic A allele was present on 63 chromosomes (frequency 0.16). The genotype frequencies were as follows: 68% (B/B), 31% (A/B) and.5% (A/A). The distribution of genotype frequencies was significantly different between the study and control groups for allele A/B heterozygotes (NOS3(A/B)) (36.7 versus 23.8%, P = 0.03, OR 1.6, 95% CI 1.1--3.8). Only one individual was homozygous for the A allele (NOS3(A/A)). She was in the study group. Between women with primary and secondary recurrent miscarriages, no statistically significant difference between the distribution of NOS3(A/B) genotypes (28 versus 34%) was observed. CONCLUSIONS: These data support a role for the NOS3 gene as a genetic determinant of the risk of idiopathic recurrent miscarriage.
Carbon monoxide, a gaseous activator of soluble guanylyl cyclase formed by a subtype of the enzyme heme oxygenase designated heme oxygenase-2 in vascular endothelium, has been found to dilate blood vessels independently from nitric oxide. Because of the parallels between nitric oxide and carbon monoxide, we speculated that estrogen might affect carbon monoxide production in vascular endothelium. Endothelial cells of human origin (umbilical vein and uterine artery) were incubated for 4 or 24 h with 10(-12)-10(-6) M 17beta-estradiol. 17beta-Estradiol, at a concentration such as that attained during the ovulatory phase of the menstrual cycle (10(-10) M), administrated for 4 h led to a 2-fold increase in intracellular carbon monoxide production and heme oxygenase-2 protein levels (P < 0.05). A reporter assay, measuring the formation of cGMP as the direct product of carbon monoxide-induced activation of soluble guanylyl cyclase in endothelial cells, also revealed a 56% increase in cellular cGMP after treatment with 10(-10) M E2 17beta-estradiol (P < 0.05). By contrast, higher 17beta-estradiol concentrations had no significant respective effects due to nitric oxide synthase inhibition of carbon monoxide release. This 17beta-estradiol effect appeared to be ER dependent, as preincubation with tamoxifen (10(-6) M) blocked the stimulatory effect of 17beta-estradiol in each instance. Our preliminary data indicate a potential role for carbon monoxide as a biological messenger molecule in estrogen-mediated regulation of vascular tone.
OBJECTIVE: Patient's acceptability, compliance, and effectiveness of a new sequential hormone replacement regimen containing 2 mg 17beta-estradiol and 10 mg dydrogesterone, were assessed in a 3-month, open, multicentre study involving 110 menopausal women. METHODS: A specially designed menopause score was used to assess the severity of menopausal symptoms, each symptom being graded at baseline and after 3 months on a four-point scale. Bleeding data were recorded by the patient on a diary card. Serum hormone levels including FSH, LH, E2, P, PRL, DHEA-S, T, SHBG were checked at the initial visit and at the end of the study. RESULTS: After 3 months of treatment, all but four of the 34 climacteric symptoms investigated showed a significant improvement. There were no significant changes noted in body weight. The average duration and flow of bleeding showed no significant changes during hormone replacement therapy (HRT). There were no serious adverse events related to treatment. CONCLUSION: The 17beta-estradiol/dydrogesterone combination HRT reduced effectively climacteric symptoms, showed no significant changes in endometrial thickness as determined by transvaginal ultrasonography and provided excellent cycle control.
There is little information about the interaction between melatonin, sexual steroids and neuroendocrine system in postmenopausal females, even if former research showed that melatonin is clearly involved in human physiology and pathophysiology. We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin (6-SMT) using a radioimmunoassay in 60 postmenopausal women. The group has been divided into patients with insomnia (10), hyperprolactinemia (7), depression (9), obesity (7) and controls (27). Compared to controls 6-SMT values were significantly higher in depressive females. Patients with hyperprolactinemia showed a trend toward a significantly elevated average nocturnal melatonin concentration. Melatonin levels were significantly lower in patients with insomnia and obese postmenopausal females than in controls. Since previous studies described lower melatonin levels in postmenopausal than in premenopausal women, the indication of melatonin therapy, especially for sleep disorders in this collective, can be handled more generously. Melatonin should be prescribed restrictively in patients with depression and in those with hyperprolactinemia. The role of melatonin in obese females remains unclear.
A search of past and current articles on ovarian physiology and premature ovarian failure (POF) using MEDLINE was performed in order to present an overview of clinical manifestations, necessary laboratory investigations, possible etiologies and treatments for POF. POF is defined as gonadal failure before the age of 40 years. Initially, POF was thought to be permanent, but it is now believed that spontaneous remissions and even pregnancies are possible in affected women. In most cases, the etiology of POF remains elusive, but several rare specific causes have been identified. Although the etiology of POF is heterogenic, the treatment principles are the same. Hormone replacement therapy (HRT) is still the cornerstone of treatment. The only proven method of obtaining a pregnancy in patients with POF is fertilization of a donor oocyte. Cryopreservation of oocytes has worked well in animals but awaits refinement before it can be applied routinely to humans with prodromal POF, or to patients before chemotherapy or irradiation in order to save their oocytes for future fertilization. New alternatives to traditional HRT and methods of fertility preservation are under development, but understanding of the basic pathophysiology of POF is necessary for the development and use of innovative treatments.
The diversity of function that sex steroids have proven to have in the female body, gives them a position of central importance in gynaecology. Scientific research demonstrates not only the well known genital functions of sexual steroids, furthermore, various extragenital organs are influenced and modulated by ovarian hormones. Therefore, the general benefit of HRT for the female organism becomes clearer and the clinical management of menopause is developing to a broad new discipline, the gender specific medicine. In clinical practise, phytosteroids are claimed by the patient and therefore, also of high interest for the scientific research. Also, tissue specificity of the endocrine treatment and the biological relevance of different steroid receptors of HRT are discussed, leading to the development of new HrT preparations. Individualisation, the tailoring of HRT, according to the patients needs, and low dose steroids management, will also become an important aspect in the recommendations for estrogen and progestin replacement therapy.
INTRODUCTION: Psychological instability as a result of changing hormone levels are commonly observed during menopause. We examined the question whether the prescription of psychotropic drugs is related to age or gender and whether the increase in the prescription rate of hormone substitutes has an impact on this phenomenon. METHODS: Age and gender-specific prescription rates of psychotropic drugs and hormone substitutes were examined in a retrospective study using data of the European Pharmaceutical Market Research Association of Austria. The relevant Austrian figures were established on the basis of representative samples. RESULTS: There are no gender-specific differences in terms of prescription frequency up to the age of 45 years. After the age of 45, there is a significant increase in the prescription of psychotropic drugs for women. When comparing the years 1991 and 1996, we find a reduction in the number of prescriptions of psychotropic drugs and an increase in the prescription rate of hormone replacement drugs. DISCUSSION: An increase in the prescription rate of hormone substitutes may contribute to the psychological stabilisation of menopausal women and thereby reduce the need for psychotropic drugs.
OBJECTIVE: It has been suggested that exposure to relatively high levels of unopposed estrogen is a risk factor for endometrial cancer. Combined therapy of estrogen with cyclic progestagen was therefore highly recommended for menopausal women with an intact uterus. METHODS: The cases of two postmenopausal women who developed endometrial cancer after taking continuous sequential HRT for 15 months are reported. Both were without bleeding for more than 2 years and presented with a normal vaginal ultrasound. They had severe menopausal symptoms and asked for HRT. RESULTS: After 15 months irregular bleeding occurred and a hysterectomy was performed. The pathohistological finding in both cases was endometrial cancer. As we measured the serum estradiol levels 4 h after tablet ingestion supraphysiologic values ranging between 418 and 442 pg/ml were found. CONCLUSION: Our report strengthens the evidence that supraphysiologic estradiol levels despite combination with cyclic progestagen therapy, increase the risk of endometrial cancer.
OBJECTIVE: To evaluate a computer-assisted technique for objective and sensitive monitoring of facial hair growth. DESIGN: Prospective study. SETTING: Department of Gynecological Endocrinology and Reproductive Medicine and Clinic for Ear, Nose, and Throat, General Hospital, University of Vienna, Vienna, Austria. PATIENT(S): Four men, three hirsute women, and three nonhirsute women. INTERVENTION(S): Using video equipment and computer software, we were able to document, analyze, and store data regarding hair growth in specific areas of interest. For digital image analysis, we used the Digi Trace System (Olympus, Vienna, Austria; Imatec, Munich, Germany). MAIN OUTCOME MEASURE(S): Hair growth within 20 days in well-defined regions of interest on the faces of hirsute and nonhirsute women and of men. RESULT(S): Hair growth on day 21 was significantly different between hirsute and nonhirsute women as well as in men. The scores for individual hair growth between day 0 and day 21 also were significantly different in hirsute women and in men. No statistically significant difference in hair growth was found within the group of nonhirsute women. CONCLUSION(S): With digital image analysis, facial hair growth, especially in hirsute women, can be calculated in a sensitive and objective manner.
OBJECTIVES: In 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study. METHODS: The inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy. RESULTS: Therapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume. CONCLUSIONS: Our results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.
Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS+ epithelial cells or total epithelial cells was 69+/-16% (n = 50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62+/-20% (n = 40), compared to 12+/-9% (n = 40) in samples of grade III carcinomas (P<0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n = 4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumor's metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.
Expression of inducible nitric oxide synthase (iNOS) and its cellular localization was investigated in subcutaneous or lymph node metastases of human melanoma. Immunohistochemistry revealed that iNOS expression was limited to melanoma cells. In samples of patients without distant metastases, the number of iNOS+ tumour cells/total tumour cells was 55% +/- 17% (n = 12) compared with 9% +/- 8% when distant metastases of lung, liver or brain occurred within an observation period of 3 years (n = 10) (P < 0.001). Western blotting confirmed the expression of iNOS protein in select cases. Notably, iNOS is expressed in regional melanoma metastases and its expression is inversely related to the tumour's metastatic potential. Thus, iNOS expression may have predictive value for the development of distant metastases of human melanoma.
OBJECTIVE: To compare the thickness of the layers of the carotid artery wall in pregnant and fertile non-pregnant women. DESIGN: Prospective cross-sectional study. SUBJECTS: Fifty-one pregnant women at a mean gestational age of 38.9 weeks and 64 fertile non-pregnant women were examined at a University hospital. METHODS: The three layers (adventitia, media, intima) of the superficial wall of the left common carotid artery were identified and measured with high-resolution ultrasound (22.5 MHz). RESULTS: Pregnant women had a thinner intima layer (0.25 +/- 0.07/0.29 +/- 0.08 mm) and a thicker media layer (0.31 +/- 0.08/0.27 +/- 0.09 mm) compared with controls. A statistically significantly higher intima/media ratio was calculated for the pregnant women (1.14 +/- 0.03), compared with the non-pregnant women (0.88 +/- 0.04). CONCLUSION: There are differences in the thickness of the histological layers of the carotid artery wall in pregnant compared with non-pregnant women. This is likely to be due to the effect of different estradiol levels in these two groups.