Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects.

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.

Short-term effects of topical testosterone in vulvar lichen sclerosus.

OBJECTIVE: To evaluate the systemic and therapeutic effect of topical testosterone treatment in vulvar lichen sclerosus. METHODS: This prospective clinical, single-arm study included ten postmenopausal women with vulvar lichen sclerosus. Testosterone propionate (0.04 g daily) was administered topically for 4 weeks. Serum androgens (testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate) were determined before and after 4 weeks of treatment, and vulvodynia was evaluated by a horizontal visual analogue scale. RESULTS: Serum levels of total testosterone increased in all patients (P < .01) and exceeded normal range in eight of ten women. Vulvodynia improved in nine of ten patients (paired t test: P < .01). Four of ten patients showed clinical signs of hyperandrogenism (enlargement of the clitoris, alterations of the voice, increase in libido) after 4 weeks of treatment. The only patient without subjective improvement had elevated basal serum androgen levels and showed clinical signs of hyperandrogenism before therapy. CONCLUSION: Topical testosterone is effective in normoandrogenic women with lichen sclerosus. Androgen status should be evaluated before treatment, and dosage should be individualized to avoid virilization and metabolic side effects. Because there is a marked systemic effect, clinical controls and a follow-up with evaluation of serum testosterone levels are recommended. Other steroids should be included in therapeutic decisions.

Effects of tibolone on auditory brainstem responses in postmenopausal women--a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the influence of tibolone, a synthetic steroid, in modifying auditory brainstem response (ABR) in postmenopausal women. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient menopausal clinic in a university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Administration of either tibolone or placebo for 12 weeks; evaluation of ABR and hormone levels before and after treatment. MAIN OUTCOME MEASURE(S): Changes in auditory brainstem response latencies. RESULT(S): Comparison of the ABR latency data from the two treatment groups showed a significant decrease in wave II, III, and V peak latencies in women receiving tibolone. No significant differences in pretreatment and posttreatment circulating hormone concentrations were observed between the tibolone and placebo group. Furthermore, there was no significant increase in hormone levels in either of the groups at 12 weeks. CONCLUSION(S): Our findings show an improvement in auditory function via brainstem auditory neural pathways sensitive to tibolone in postmenopausal women. Tibolone may offer new therapeutic strategies in otologic disorders.

Computerized assessment of facial hair growth.

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.

Topical cyproterone acetate treatment in women with acne: a placebo-controlled trial.

OBJECTIVE: To evaluate the clinical and hormonal response of topically applied cyproterone acetate, oral cyproterone acetate, and placebo lotion in women with acne. DESIGN: Placebo-controlled, randomized study. SETTING: Patients were recruited from the Institute of Endocrine Cosmetics, Vienna, Austria. PATIENTS: Forty women with acne. INTERVENTIONS: Treatment with oral medication consisting of 0.035 mg of ethinyl estradiol and 2 mg of cyproterone acetate (n=12), 20 mg of topical cyproterone acetate lotion (n=12), and placebo lotion (n=16) was offered. Patients were assessed monthly for 3 months. MAIN OUTCOME MEASURES: Clinical grading according to acne severity and lesion counts as well as determinations of serum cyproterone acetate concentrations. RESULTS: After 3 months of therapy with topical cyproterone acetate, the decrease of mean facial acne grade from 1.57 to 0.67 was significantly better (P<.05) compared with placebo (which showed a change from 1.57 to 1.25), but not compared with oral medication (1.56 to 0.75) (P>.05). Lesion counts also decreased from 35.9 to 9.1 in the topical cyproterone acetate group compared with oral medication (45.4 to 15.5) (P>.05) and placebo (38.2 to 23.1) (P<.05). After topical cyproterone acetate treatment, serum cyproterone acetate concentrations were 10 times lower than those found after oral cyproterone acetate intake. CONCLUSIONS: The therapeutic effect of topically applied cyproterone acetate for acne treatment was clearly demonstrated. Topically applied sexual steroids in combination with liposomes are as effective as oral antiandrogen medication in acne treatment, while reducing the risk of adverse effects and avoiding high serum cyproterone acetate concentrations.

Treatment of keratoconjunctivitis sicca with topical androgen.

OBJECTIVE: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported. METHODS: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy. RESULTS: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT. CONCLUSION: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.

Clinical profile of a new hormone replacement therapy containing 2 mg 17 beta-estradiol and 10 mg dydrogesterone.

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.

Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women.

OBJECTIVES: This study was carried out to assess the effect of topical androgen replacement therapy on body weight, body composition and fat distribution in postmenopausal women. METHODS: 39 healthy postmenopausal women (51.4 +/- 2.24 years), with increasing body weight, were prospectively studied for 6 months. Body composition (fat mass, kg, %) was measured by means of dual-energy X-ray absorptiometry (DXA). Hormonal and lipid parameters were also measured. Subjects were divided into two groups. An androgen gel (group A) or placebo gel (group P) was topically administered to the abdominal and gluteo-femoral regions. DXA was performed before commencement of topical treatment and after 6 months. RESULTS: A highly significant total body weight reduction was found in group A (68.0 +/- 13.1 to 65.4 +/- 11.8 kg). Abdominal fat (37.3 +/- 11.2 to 35.1 +/- 9.7%), gluteo-femoral fat (46.3 +/- 6.6 to 45.4 +/- 7.7%), total body fat (38.2 +/- 7.9 to 36.1 +/- 8.6%) and BMI (24.8 +/- 4.3 to 23.7 +/- 3.8) were also found to have decreased significantly in this group. No significant reduction in body weight (kg) and body fat (%) could be measured in the placebo group. No influence on lipid parameters was found although total testosterone increased significantly in group A (0.29 +/- 0.24 to 0.72 +/- 0.17 ng/ml). CONCLUSIONS: Topically applied androgen is capable of reducing abdominal fat accumulations as well as total body weight in postmenopausal women with unexplained weight gain. In contrast to systemic androgen application, topical administration has no effect on the lipid profile. Gluteal fat, however, is less effectively influenced by androgens.

The influence of hormone replacement therapy on skin ageing: a pilot study.

OBJECTIVES: We studied the effect of hormonal treatment on skin ageing in menopausal women. METHODS: Twenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone. RESULTS: Mean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH. CONCLUSIONS: HRT with the mentioned regimes significantly improved parameters of skin ageing.

Endometrial cancer after combined hormone replacement therapy.

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.

Hormone replacement therapy and intraocular pressure.

OBJECTIVES: To evaluate the effect of hormone replacement therapy (HRT) on intraocular pressure (IOP) in menopausal women. METHODS: The IOP of 25 white menopausal women without an abnormal ophthalmologic history was measured before and during HRT regimen. IOP fluctations were recorded before and 1, 4, and 12 weeks after the beginning of HRT. These measurements were obtained according to a standardized time schedule (08:00, 12:00, 16:00, and 19:00 h). RESULTS: The mean IOP in the left eye decreased from 16.2 +/- 2.4 mmHg before therapy to 14.0 +/- 2.1 mmHg after 12 weeks of therapy (P < 0.001). In the right eye, whose IOP was at 15.3 +/- 2.3 mmHg before therapy there was a decrease to 14.0 +/- 1.9 mmHg after 12 weeks of therapy (P < 0.001). CONCLUSION: Hormone replacement therapy has a positive effect on IOP in menopausal women.

The effect of hormone replacement therapy on carotid arteries: measurement with a high frequency ultrasound system.

OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on carotid arteries in postmenopausal women with a high frequency ultrasound system. METHODS: In a clinical cross-sectional study carotid artery layers were measured in 82 postmenopausal women receiving a sequential regimen of HRT (oestradiol valerate 2 mg and dydrogesterone 10 mg) and in 70 postmenopausal women without HRT. Measurements of the left carotid artery layers (externa, media, intima) were taken with a single mechanically activated 22.5-MHz transducer with an effective band width of 8 MHz. RESULTS: A statistically significant increase in thickness of the media layer of the carotid artery was observed in the HRT group (0.34 +/- 0.06 mm) as compared to the untreated group (0.27 +/- 0.03 mm). The media/intima ratio of the treated group was statistically significantly higher than that of the untreated group (P < 0.05). The mean strength of the carotid wall was 0.70 +/- 0.17 mm in the 70 postmenopausal women without HRT and 0.76 +/- 0.24 mm in the 82 patients undergoing HRT. CONCLUSION: HRT has a morphological effect on the carotid arteries in postmenopausal women. These findings support a cardioprotective effect, especially in terms of prevention of atherosclerosis. This effect can be measured non-invasively by high frequency ultrasound.

Reduction of intraocular pressure in a glaucoma patient undergoing hormone replacement therapy.

OBJECTIVES: To show the reducing effect of estrogens and progestins on the elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing typical climacteric complaints, who was admitted to the menopause outpatient unit. She also suffered from a primary open-angle glaucoma treated with betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local therapy. METHODS: IOP patterns were monitored by means of standardised daily pressure profiles four times a day before as well as 4 and 12 weeks after the beginning of hormone replacement therapy (HRT). The local glaucoma therapy remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the beginning of HRT. CONCLUSION: The finding of a close chronological relationship between the onset of menopause and the development of a glaucoma is a potentially new indication for HRT.

Differentiating vulvar intraepithelial neoplasia from nonneoplastic epithelial disorders. The toluidine blue test.

OBJECTIVE: To determine the effectiveness of the toluidine blue test in the differentiation of vulvar intraepithelial neoplasia (VIN) and nonneoplastic epithelial disorders (NNEDs). STUDY DESIGN: This retrospective clinical study included all women with VIN (n = 24) and NNED (n = 72) referred to a vulvar clinic at a university hospital during a two-year period. Vulvoscopy, staining of vulvar epithelium with 1% toluidine blue and punch biopsy were performed. RESULTS: Vulvar epithelium demonstrated toluidine blue staining in 100% of the patients with VIN 3, in 83% of women with VIN 1-2, in 50% of the women with squamous cell hyperplasia and in 10% of the women with lichen sclerosus. The differences in staining between the groups were statistically significant (P < .001). The sensitivity of toluidine blue staining for the detection of VIN was 92%; the negative predictive value 96% in teh investigated cohort. The specificity for strong staining was 88%. CONCLUSION: The toluidine blue test is an inexpensive and reliable method of separating VIN from hyperplastic NNED areas and choosing a biopsy site on the vulva.

Serum levels of progesterone in patients with preeclampsia.

In a matched pair-study study we investigated the hitherto controversially discussed serum levels of progesterone in 40 women with severe preeclampsia (PE) and 40 normotensive controls. Serum levels were determined by applying a sandwich enzyme-linked immunosorbent assay (ELISA). Median serum levels of progesterone in preeclamptic women and in controls were not statistically significant (P = 0.73). Our study indicates that the absence of altered serum levels of progesterone may not reflect the potential role of this hormone in preeclampsia.

[Epidemiology and clinical value of true umbilical cord knots]. / Epidemiologie und klinische Wertigkeit von echten Nabelschnurknoten.

OBJECTIVE: To evaluate the epidemiology of true knots of the umbilical cord and their impact on pregnancy outcome. MATERIALS AND METHODS: 22531 singleton deliveries were included in this retrospective study (1976-1994). Newborns with malformations were excluded. The database of the 2nd Department of Obstetrics and Gynaecology, Vienna University Hospital was analyzed. RESULTS: The incidence of true knots was 1.27% (n = 286). Multiparous women are more likely to give birth to a child with a true knot of the umbilical cord than primiparae (1.52% vs. 1.01%, P < 0.001). Male fetuses are more frequently affected than females (1.49% vs. 1.04%, P = 0.01). Duration of pregnancy, fetal weight, presentation and mode of delivery are not significantly influenced by umbilical knots. Fetal acidosis (pH < 7.10) was more common in the cohort with true knots as compared with the controls (8.33% vs. 4.03%, P < 0.01). Apgar score and transfer rate to a neonatal unit were not influenced. Still-births were more common in the cohort with umbilical knots (1.7% vs. 0.6%, P < 0.05); there was no neonatal death in the cohort with true knots, however. CONCLUSION: A fetus with a true knot of the umbilical cord is at risk for fetal death. During labour umbilical knots have no adverse effect on pregnancy outcome.

[6-sulfatoxymelatonin in women with secondary amenorrhea]. / 6-Sulfatoxymelatonin bei Frauen mit sekundärer Amenorrhoe.

We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin in a group of 347 women (range: 18-69 years). 26 women (range 20-29 years) with normogonadotrophic, hypoestrogenemic amenorrhoea (WHO II) were selected and compared with a group of 26 women menstruating normally (range: 19-30 years) with respect to urinary 6-sulfatoxymelatonin excretion, serum 17 beta-estradiol levels and response to the thyroid releasing hormone (TRH) test. Patients with hyperprolactinemia, hyperandrogenemia, thyroid dysfunction and weight problems were excluded. 6-sulfatoxymelatonin was found to be significantly higher in the amenorrhoeic women than in the controls (p < 0.000001). In the amenorrhoeic patients a statistically significant inverse correlation was found between serum 17 beta-estradiol levels and urinary 6-sulfatoxymelatonin excretion. A positive correlation was obtained between the thyroid stimulation hormone (TSH) value measured at 20 minutes after stimulation and 6-sulfatoxymelatonin excretion. Further clinical research in this field is required to evaluate its clinical impact, especially in patients with secondary amenorrhea.

[The clinical value of 3 alpha-androstanediol-glucuronide in hirsute women]. / Die klinische Wertigkeit von 3 alpha-Androstanediol-Glucuronid bei hirsuten Frauen.

Aim of this prospective diagnostic study was to determine the serum 3 alpha-androstanediol-glucuronide (AdiolG) level in hirsute women in order to assess the androgenic activity in peripheral tissue and to differentiate between hirsutism of peripheral origin and that of adrenal or ovarian origin. Diagnostic advantages might have been expected in patients with idiopathic hirsutism, in whom increased 5 alpha-reductase activity may be reflected by this parameter. Apart from serum AdiolG, we determined the established parameters testosterone, androstendione and dehydroepiandosterone sulfate in 63 hirsute premenopausal women and in 51 non-hirsute controls. AdiolG (P < 0.05), as well as the 3 established parameters (P < 0.001) were elevated in the hirsute women as compared with the controls; however, the subgroup of women with idiopathic hirsutism (n = 32) showed no elevation of serum AdiolG. Analysis of the combined hirsute and control groups showed that the correlation of AdiolG to the hirsutism score (r = 0.42) was markedly weaker than that of testosterone to the latter (r = 0.62). Moreover, no correlation was found between the body-mass index and AdiolG. Our data show that serum AdiolG is obviously not a specific marker for peripheral 5 alpha-reductase activity, but appears to reflect the adrenal and ovarian androgen precursors. Thus, determination of serum AdiolG is of no diagnostic benefit in the clinical assessment of hirsute women.

Trends in the prescription of psychotropic drugs and hormone substitutes in Austria.

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.

A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women.

BACKGROUND: There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging. OBJECTIVE: In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women. METHODS: Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17beta-estradiol/10 mg dydrogesterone (Femoston) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated. RESULTS: After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right upper arm (inner side); skin thickness improved significantly but skin surface lipids did not. Absolute effects did not differ significantly between HRT and placebo patients. A dermatological evaluation was largely consistent with measurement results. Safety and tolerability of HRT were positive. CONCLUSION: The results showed improvements in the parameters involved in skin aging in the HRT group as compared to baseline. While skin aging is no indication for systemic hormone supplementation, a positive effect on aging skin can be observed.