Comparison of the effect on acne with a combiphasic desogestrel-containing oral contraceptive and a preparation containing cyproterone acetate.

OBJECTIVE: To investigate the effect of a combiphasic oral contraceptive containing ethinylestradiol and desogestrel (combiphasic EE/DSG) on acne, compared with a preparation containing ethinylestradiol and cyproterone acetate (EE35/CPA). METHODS: An open, randomized, group-comparative, multicenter study was carried out, with 172 women randomized to treatment with either combiphasic EE/DSG (25 microg desogestrel and 40 microg ethinylestradiol for 7 days followed by 125 microg desogestrel and 30 microg ethinylestradiol for 15 days) or EE35/CPA (2.0 mg cyproterone acetate and 35 microg ethinylestradiol for 21 days). Assessments were performed at pretreatment and after cycles 3 and 6. RESULTS: The number of comedones, papules, pustules and nodules significantly decreased in both groups over the 6-month study. Compared with pretreatment (= 100%), the relative numbers of comedones, papules, pustules and nodules at cycle 6 significantly decreased to 37%, 38%, 19% and 12.5% in the combiphasic EE/DSG group and to 24%, 36%, 17% and 1% in the EE35/CPA group, respectively. All reductions were statistically significant (p < or = 0.003) at both cycles 3 and 6, except for nodules at cycle 6 with combiphasic EE/DSG, which probably resulted from differences between the treatment groups at baseline. There were no statistically significant differences between the two treatments. In both groups, the majority of women with severe acne shifted to a less severe acne category. CONCLUSIONS: Combiphasic EE/DSG progressively reduced the number and severity of acne lesions during the six cycles of treatment. The reduction in acne with the combiphasic oral contraceptive was comparable to a preparation containing the antiandrogen cyproterone acetate.

[Effect of combined conjugated estrogen-medrogestone replacement therapy on lipid profiles, climacteric symptoms and the endometrium]. / Effets sur les lipides, les symptômes climatériques et l'endomètre d'une association d'estrogènes conjugués et de médrogestone dans le traitement hormonal substitutif.

OBJECTIVE: To assess the effects of continuous administration of conjugated estrogen combined with sequential administration of medrogestone on lipid profiles, climateric symptoms and endometrial tolerance. METHODS: This multicenter open study was conducted for one year to assess the effects of a hormone replacement therapy (HRT) regimen using Premarin (0.625 mg/day 28d/28) combined with medrogestone 5mg for 12 days (d17-d28 of each 28-day cycle) on lipid profiles, climateric symptoms and cycle control in 228 post menopausal women with an intact uterus. The subjects were recruited in 23 centers in 7 countries in Europe and Asia. Serum lipid/lipoprotein levels were determined at baseline and at cycles 3, 6, 13; endometrium biopsies were performed at screening then at cycle 13. Climateric symptoms and bleeding patterns were recorded by the patients from daily diaries cards collected at baseline and at visits during cycle 3, 6, 9, and 13. RESULTS: By cycle 3, the conjugated estrogen-medrogestone combination induced significant modifications of the lipid profile which were judged favorable. These modifications were maintained throughout treatment. All the baseline values were within normal limits. Mean variations compared with baseline values (expressed in mmol/l) after cycles 3, 6, and 13 were -0.46, -0.54, and -0.46 for total cholesterol (p<0.05), + 0.053, + 0.057, and + 0.078 for HDL-cholesterol (p<0.05) and -0.556, -0. 542, and -0.493 for LDL-cholesterol (p<0.001) respectively. VLDL-cholesterol levels were unchanged. Triglycerides increased significantly though moderately: + 0.12, + 0.15, and + 0.15 mmol/l at cycles 3, 6, and 13 respectively. Endometrial biopsies obtained at cycle 13 (n=195) did not reveal any endometrial hyperplasia. Withdrowal bleeding was predictable for a 6 to 7.4 day interval. The incidence of irregular bleeding varied from 7 to 33% and decreased progressively over the 13-cycle treatment. The incidence of amenorrhea increased from 14 to 52% over the 12 months studied. Finally, at each cycle, menopausal symptoms (mean number of hot flushes/day and Küpperman score) were significantly improved compared with the baseline. As expected, modifications were more pronounced after cycle 1, but improvements were maintained throughout the study. CONCLUSION: Continuous administration of Premarin in combination with sequential administration of medrogestone was found to be an effective treatment for menopausal symptoms. It was associated with favorable modifications of the lipid profile and was safe for the endometrium.

Interruption of aortic arch and hypoplastic left heart syndrome.

Interruption of the aortic arch and hypoplastic left heart syndrome in the same patient is exceptional. In the combined collections of the Registry of Cardiovascular Disease (St. Paul, Minnesota, U.S.A.) and the Registry of Congenital Heart Defects of the Rijksuniversiteit Gent (Gent, Belgium) three specimens were found with this unusual combination. These cases are herein described and compared with four similar cases previously reported in the literature.

Metoclopramide and breast milk.

Thirteen primiparous nursing mothers participated in this placebo-controlled double blind trial of metoclopramide. Therapy was started on the first postpartum day and continued for 8 days. Seven women received metoclopramide (10 mg, 3 X dd). Serum prolactin and milk yield were measured during the trial. The breast milk composition was analysed during the trial and weekly for 3 wk after the trial. A detailed analysis of the amino acid content was performed on the 6th and 21st postpartum days. During the early puerperium the total milk yield was ca. 50% greater in the metoclopramide-treated group compared to the control group. The evolution of the breast milk composition was similar for both groups, except for the amino acid content. The shift in amino acid composition occurred earlier in the treatment group indicating that metoclopramide enhances the rate of transition from colostrum to mature milk.

Comparison of breast tumours evaluated by ultrasound, mammography, and clinical investigation.

One hundred eleven palpable breast tumours were evaluated clinically, by mammography, and by ultrasound; upon histological examination 51 of the tumours turned out to be malignant and 60 benign. In 44 tumours, which appeared malignant on the ultrasound scan, the axilla was also scanned and the findings were compared with the results of histological examination of excised lymph nodes. The diagnostic accuracy for malignancy of breast tumours was 86.3% for ultrasound scans, 80.4% for mammography, and 78.4% for clinical evaluation; the respective diagnostic accuracy for benign lesions was 88.3%, 85%, and 91.7%. Of 36 enlarged reactive or malignant lymph nodes, 32 were detected by ultrasound and only 18 by clinical examination.

Prostaglandin F2 alpha for interrupting pregnancy, managing intrauterine death and molar pregnancy and inducing labor.

Serial intramuscular injections of 250 microgram of 15 (S), 15-methyl-prostaglandin F2 alpha were given to 105 women every 1-3 hours in an attempt to induce second-trimester abortion (N = 80) or labor (N = 25), the latter because of late intrauterine death or anencephaly. The treatment was highly successful; the cumulative expulsion rates at 12 and 24 hours were 69% and 95%, respectively. There were no serious complications, and significant alterations in the mother's vital signs were uncommon. Gastrointestinal side effects are tolerable if the woman is properly premedicated and maintained on the antiemetic, antidiarrheic and analgesic treatments.

PIP: Serial intramuscular injections of 250 mcg of 15(S,15-methyl-prostaglandin F2alpha were given to 105 women every 1-3 hours in an attempt to induce second trimester abortion (N=80) or labor (N=25). Patients were divided into 5 groups: those with missed abortions; those with pregnancy terminations; those with molar pregnancy; those with intrauterine death; and those where labor was induced with a live anencephalic fetus. The treatment was highly successful; the cumulative expulsion rates at 12 and 24 hours were 69% and 95% respectively. There were no serious complications, and significant alterations in the mother's vital signs were uncommon. Gastrointestinal side effects are tolerable if the woman is properly premedicated and maintained on the antiemetic, antidiarrheic, and analgesic treatments.

The effect of locally administered estrogens on the human cervix.

A randomized study to evaluate the effect of natural estrogens on the unripe uterine term cervix was conducted. One hundred and five term gravidas were studied, of whom 70 were treated with 180 mg 17 beta-estradiol or 250 mg estriol (treated women) and 35 were treated with gel only (control group). In all subjects the distented Foley catheter used for the instillation was left in situ. Twelve hours after the instillation there was no apparent difference in mean cervical progress between treated women and controls and the rather unexpected degree of cervical ripening is atributed to the intra-uterine balloon catheter. The procedure could not be shown to have any untoward effect on the mother or the fetus.

Puerperal lactation suppression and prolactin.

Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment.

Pre-induction ripening of the cervix with extra-amniotic prostaglandin E2 in gel.

Pre-induction ripening of the unfavorable cervix was attempted in 104 normal term gravidas by means of a single extra-amniotic instillation of a viscous gel containing 0.5 mg prostaglandin E2. The procedure was highly successful and no adverse effect on mother or fetus was observed.

[Tubal sterilization by minilaparotomy]. / Tubasterilisatie via minilaparotomie.

PIP: A study of methods, techniques, and instruments used in surgical contraceptive procedures from approximately 1965-1978, makes the assertion that the ideal sterilization technique still has not been invented, while at the same time noting that transcervical and transuterine sterilizations are still in the research stage, and tubal sterilization has attained considerable popularity as an everyday practice. Passing attention is given to culdotomy, culdoscopy, laparoscopy, and laparotomy, while stressing minilaparotomy as the current most widely used means of female sterilization. An overview of the history of the minilaparotomy is presented, as well as the results of a study conducted from February 1976 to December 1977 at the Gynecological Clinic in the Academy Hospital in Hoofden involving 102 nonpregnant women who received minilaparotomies. Of the participants, who were aged 19-47 (average age 35 and average parity 2.7), 80 were sterilized electively, and 22 medically. The length of incision varied from 1-6 cm; the average length of operation was 31 minutes; the period for recovery from flatus was 0-3 days; and the average length of stay in a clinic 3.2 days. Morbidity figures were low, the most frequent wound complication being hematoma (3%); this agrees with reports in the literature since 1976 of nonlethality in 17,500 minilaparotomy sterilizations.^ieng

Extra-amniotic prostaglandin F2alpha in gel for prelabor cervical ripening.

In 22 normal term gravidas with unfavorable cervix, 5 mg PGF2alpha in Tylose gel was instilled into the extra-amniotic space. The treatment improved the cervical state so much that the women could be successfully induced by conventional methods. The procedure was well tolerated by the mother and it appeared to be perinatally safe.

Modulation of pituitary responsiveness to exogenous LHRH by an oestrogenic and an anti-oestrogenic compound in the normal male.

The effect of clomiphene (100 mg daily for 10 days) and ethinyl oestradiol (100 mug daily for 10 days) on the gonadotrophin response to synthetic LHRH has been investigated in two groups of five normal males. A third group of five men served as control group. LHRH, 25 mug, was injected intravenously on days 0, 4, 7 and 10 and the response of serum LH and FSH was monitored by radioimmunoassay. In contrast to the wide inter-individual variation of the response pattern, the intra-individual variation of the response to LHRH in the control group was small. Clomiphene induced a significant elevation of the baseline levels of LH and FSH after a few days of treatment; the pituitary responsiveness to LHRH, however, was significantly reduced. Oestrogen treatment resulted in a uniform suppression of both basal gonadotrophin levels and pituitary responsiveness. The decreased gonadotrophin response to LHRH during clomiphene treatment is thought to be caused by a relative and temporary pituitary depletion of the releasable gonadotrophin content. Although the suppression of LH and FSH response during oestrogen treatment may point to a direct inhibitory effect of oestrogen on pituitary gonadotrophin release, an indirect hypothalamic pathway, through suppression of endogenous LHRH, cannot be ruled out.