[Acceptability of continuous combined versus cyclical HRT: a French multicentric randomized clinical study]. / Acceptabilité par les patientes d'un THS combiné continu versus cyclique: une étude clinique randomisée multicentrique française.

OBJECTIVES: To describe and compare acceptability of treatment and quality of life over 12 cycles in 2 groups of women randomised to continuous combined Climodiène (estradiol valerate 2 mg/dienogest 2 mg) or cyclic Climène (estradiol valerate 2 mg, from D1 to D21/cyproterone acetate 1 mg, from D12 to D21, followed by 7 days off), switching from previous sequential estroprogestative HRT because of side effects. PATIENTS AND METHODS: One hundred forty three postmenopausal women aged 54.39-years were recruited and randomised to Climène (N=68) or Climodiène (N=75). Acceptability was evaluated by the continuation rate in the 2 groups at the end of the 12 cycles study. Assessment of quality of life was obtained from the responses to the women's health questionnaire (WHQ) and to an ad hoc satisfaction questionnaire at baseline, and at the 12th cycle of treatment. RESULTS: No significant difference in baseline characteristics of volunteers were found in the 2 treatment groups except for the socioeconomic status (more town-dwellers in Climène group). Total WHQ score significantly improved after 12 months of treatment with Climène and Climodiène, respectively decreasing from 68.9 to 64.37 (-4.53) and from 69.95 to 62.06 (-7.89), with a trend towards higher improvement with Climodiène, particularly in the hot flushes subscale. In Climodiène group, a significant decrease in sleep problems and cognitive function subscales was found, which is consistent with previous polysomnography and psycho physiological measures data with Climodiène. The evolution of Satisfaction Index is positive and of the same magnitude in the 2 groups, showing an improvement at 12 months: respectively -2.79 (P=0.002) et -2.26 (P=0.02) for Climène and Climodiène. DISCUSSION AND CONCLUSIONS: Even though the benefit/risk ratio of the hormonal substitutive treatment is recognized effective against climateric symptoms which affect the quality of life, this work is the first randomised prospective study on the effects of Climodiène on quality of life in post-menopausal women assessed by the French validated version of the world-wide used WHQ. Decreases in "sleep problems" and "cognitive function" subscales scores in this study are of a magnitude clinically relevant and consistent with previous data on Climodiène impact on postmenopausal symptoms.

[Acne in adult women: data from a national study on the relationship between type of acne and markers of clinical hyperandrogenism]. / Acné de la femme adulte.

INTRODUCTION: The role of hyperandrogenism in acne occurring or persisting in adult women is controversial. Studies reported have often been carried out in hospital settings. The aim of this nationwide prospective and descriptive study was to evaluate the frequency of clinical hyperandrogenism in a large number of adult acneic women visiting dermatologists in a non-hospital setting. PATIENTS AND METHODS: Three hundred and fifteen dermatologists completed clinical questionnaires concerning the next five female patients with acne at their private practices. These patients had to be between 25 and 45 years of age. The questionnaire covered patients' demographic characteristics, medical history, gynaecological status and acne history. Patients' acne, seborrhea and cycle disorders were described, as well as other signs suggesting hyperandrogenism, such as hirsutism and alopecia. RESULTS: A total of 1 135 questionnaires were analyzed. Nearly 50 p. 100 of the patients had major scalp or facial seborrhea, 18.4 p. 100 hirsutism, 7 p. 100 alopecia and 32.2 p. 100 menstrual cycle abnormalities. When these signs were present, acne was more often retentional, with more scarring and more widespread. CONCLUSION: This prospective study in a large number of patients in a non-hospital setting shows that acne in adult women is frequently associated with clinical hyperandrogenism.

[Effects of a sequential combination of estradiol valerate and cyproterone acetate on the functional properties of the arterial wall in menopausal women]. / Effets d'une association séquentielle de valérate d'estradiol et d'acétate de cyprotérone sur les propriétés fonctionnelles de la paroi artérielle des femmes ménopausées. Groupe d'étude clinique Climène paroi artérielle.

Several studies have shown that estrogen replacement therapy protects postmenopausal women against coronary artery disease. This protective effect has been ascribed to the hormone's effect on serum lipids, as well as a direct action on the vascular wall. Concurrent administration of a progestin to protect women from the risk of endometrial hyperplasia may alter the protective effects of estrogen. The aim of this study was to assess the evolution of the endothelial function in postmenopausal women given a sequential combination of oral 2 mg estradiol valerate for 11 days, followed by 2 mg estradiol valerate associated with 1 mg cyproterone acetate for ten days (Climène). Each 21-day sequence was followed by a seven-day treatment-free interval. The women received a three-month treatment course. Thirty-one healthy postmenopausal women participated in the study (median age: 51 years; range: 45-59 years). Flow-mediated dilatation (FMD), a reflection of endothelium-dependent vasomotor function, increased from 8.47% at baseline (range: 4.57-11.02%) to 9.64% (range: 7.07-13.12%) at the end of the first treatment cycle; i.e., a 15% increase over baseline (P < 0.0001). FMD further increased after three treatment cycles to 10.59% (range: 8.09-15.22%); i.e., a 28.6% increase over baseline (P < 0.0001). FMD at the end of the first combined sequence or after the 11 days of estradiol only were similar (delta = 0.25%; range: -2.31-5.81%; not significant). In conclusion, in postmenopausal women, a three-month sequential treatment combining estradiol valerate and estradiol valerate plus cyproterone acetate (Climène) has beneficial effects on endothelial function as demonstrated by the evolution of the FMD. There was no decrease in the effect of estradiol on FMD when cyproterone acetate was added to estradiol.

Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism.

The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/-17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/-17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG).

17 beta-Estradiol: oral or parenteral administration in hyperandrogenic women? Metabolic tolerance in association with cyproterone acetate.

OBJECTIVE: To compare the metabolic effects of two different administration routes of estrogen associated with cyproterone acetate (CPA) in young women. DESIGN: Randomized and prospective study. SETTING: University medical and research center. PATIENTS: Sixty-five premenopausal young women with clinical hyperandrogenism. INTERVENTIONS: A high dose of CPA was administered, associated with either transdermal (group T) or oral (group O) 17 beta-E2. MAIN OUTCOME MEASURES: Glucose tolerance, plasma lipid level, coagulation and fibrinolysis parameters, and angiotensinogen, before and at 6 and 12 months during treatment. RESULTS: At 12 months, fasting blood glucose and basal insulin levels were significantly lower in group O than in group T. The increase in angiotensinogen was greater in group O, however, without modification in arterial blood pressure. No significant difference between the two groups was observed in lipids, coagulation, and fibrinolysis. CONCLUSION: Natural estrogens associated with CPA have no patent deleterious metabolic effect. However, the choice of oral estrogen administration seems to be better among patients with disorders such as hyperandrogenism or obesity with potential hyperinsulinism.

[Acceptability, tolerance and quality of life impact of cyproterone acetate treatment in female hirsutism. Comparison of 2 protocols in combination with oral or transdermal estradiol]. / Acceptabilité, tolérance et impact sur la qualité de la vie du traitement de la femme hirsute par l'acétate de cyprotérone. Comparaison de 2 schémas l'associant soit à l'estradiol per os, soit par voie transdermique.

67 women (aged 16-40) with hirsutism and/or other signs of hyperandrogenism (acne, androgenic alopecia, cycle disturbances) have been treated for one year with cyproterone acetate + estradiol. Patients have been randomly assigned to therapy with cyproterone acetate and estradiol valerate per or cyproterone acetate and transdermal estradiol. Acceptance, tolerance and effects on quality of life of this treatment have been assessed using a self questionnaire completed with questions for assessment for compliance. Among patients who have had a full course of treatment, 54 have fulfilled the end-of-study quality of life questionnaire. The queries allow calculation of a relational well-being score and of an emotional well-being score. The answers to the initial questionnaire show in a high percentage of patients emotional trouble (depressive state, anxiety, irritability) and disturbances in relational life. The hirsutism score has been found to be significantly correlated with anxious trouble but not with the global quality of life score. The treatment has resulted in a significant improvement in acceptance of being exposed to view (p < 0.01), self-assurance (p < 0.01) as well as emotional well-being score (p < 0.05), without any significant difference between the 2 therapeutics groups. Measurement of treatment acceptance with a visual analogic scale has been found globally very satisfactory by patients from the 2 groups. Compliance of treatment with transdermal estradiol turned out to be lesser in younger patients but is better in patients in whom emotional balance has been improved by therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[The decrease in thyroid hormones in CAPD is not explained either by iodine saturation or by dialysate loss]. / La diminution des hormones thyroïdiennes en DPCA ne s'explique ni par la saturation iodée ni par la perte dans le dialysat.

Total T4, total T3 and TSH were measured in blood, urine and dialysate of 13 patients on CAPD. Iodine was measured in blood and urine. Free T4 and T3 were measured in blood only. Serum measurements revealed one true hypothyroidism, normal total T4, T3 and TSH for 12 patients, low free T4 and T3 with normal TSH for 9 patients. Iodine was slightly elevated for 3 patients. Urinary T4 and T3 were low. Dialysate T4 and T3 were low (T4 = 13, 6 nmol/24 H). Low free thyroid hormones are not relevant to iodine excess, nor to dialysate losses. Low free thyroid hormones may be considered as an endocrine dysfunction of chronic illnesses.

Prolonged refractoriness to the diabetogenic action of streptozotocin in mice.

A single intraperitoneal injection of 5 mg (250 mg/kg body wt) streptozotocin induced overt diabetes within 48 hr in male, 6-week-old mice of C57BL/6 and C57BL/10 (sensitive) strains. The C3H/HeJ and C3H/eb (resistant) strains exhibited a progressive delayed-onset hyperglycemia which required 6 weeks to reach the level seen within only 48 hr in sensitive strains. Resistance to SZ-induced diabetes was not related to changes in body weights or different pharmacokinetics of the drug. C3H/HeJ (resistant) mice showed a smaller fall in immunoreactive insulin pancreatic content and less severe damage of pancreatic islets on histologic examination, when compared to C57BL/6 (sensitive) mice during the first week post-SZ. These results suggest that strain-related resistance to SZ-induced diabetes may be mediated at the level of the beta cell's responsiveness to the cytotoxic action of the drug. This very simple experimental tool may be of value in monitoring the period before the onset of overt insulin-deficient diabetes and for probing the nature of factors that constitute a genetically resistant pancreas, understanding of which could aid management of diabetes mellitus in humans.

Localized deep microwave hyperthermia in the treatment of poor operative risk patients with benign prostatic hyperplasia.

Non-invasive localized deep microwave hyperthermia was applied as an alternative treatment to surgery in 29 patients with contraindications for prostatectomy. Patients were treated twice weekly, on Mondays and Thursdays, for 1 hour, without sedation on an outpatient basis. All patients tolerated treatment well without secondary effects. The results indicate that localized deep microwave hyperthermia applied by this method is safe and effective in the treatment of benign prostatic hyperplasia.

[Amiodarone and hyperthyroidism. Several guidemarks for the practitioner]. / Amiodarone et hyperthyroïdie. Quelques repères pour le praticien.

The prevention and diagnosis of amiodarone-induced hyperthyroidism are largely based on clinical signs: a personal or family history of thyroid disorders, or an abnormality detected on palpation of the thyroid gland, are contraindications for amiodarone treatment. At that stage it is useless to determine hormone levels, since they do not permit screening of any cell metabolism abnormality. Weight loss accompanied by tachycardia is suggestive of amiodarone-induced hyperthyroidism. Amiodarone-induced hyperthyroidism will regress in 2 to 6 months after treatment discontinuation.

[Spironolactone in idiopathic hirsutism, clinical and biological evaluation of treatment]. / La spironolactone dans l'hirsutisme idiopathique, évaluations clinique et biologique du traitement.

Ten midly hirsute women with normal serum levels of testosterone were treated with spironolactone (100 mg die), and the effectiveness of this dose-schedule regimen was evaluated after six months of therapy. Hirsutism subsided partly in all women. We estimated however, that in 6 of the 10 women, the clinical benefit was out weighed by the side effects and other drawbacks of a long term therapy and their medication was then stopped 6 months after its initiation. The changes induced on the pituitary function were evaluated by measuring basal serum T3 T4 and basal and stimulated (TRH-LHRH) TSH, PRL, FSH and LH, prior to and after one month of therapy. Spironolactone induced a greater response of TSH to TRH (p less than .025) but no change in T3 T4, PRL, FSH and LH. These data suggest that changes in TSH response are not explained by the speculated intrinsic oestrogenic activity of spironolactone but rather by a selective interaction with TSH secreting cells. We conclude that spironolactone therapy should not be recommended for the large category of normal women complaining of slight increase of facial hair.