Isosorbide mononitrate induces increased cervical expression of cyclooxygenase-2, but not of cyclooxygenase-1, at term.

OBJECTIVE: Prostaglandin and nitric oxide (NO) are both known to be involved in cervical ripening at term. The aim of the study was to investigate if NO has an effect on cervical expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the two main isoenzymes involved in prostaglandin synthesis, and to localize these enzymes within the cervix. STUDY DESIGN: Women with an unripe cervix scheduled for elective caesarean section at term were randomly selected to receive vaginally either the NO donor isosorbide mononitrate (IMN) or placebo 4h before surgery. At the operating theatre, cervical tissue specimens were obtained for immunoblotting and immunohistochemistry. RESULTS: Increased expression of COX-2 was found in specimens exposed to IMN compared to specimens obtained from women in the placebo group. There was no difference in the expression of COX-1. Immunohistochemistry revealed similar localization of the two enzymes in treated and untreated women. CONCLUSIONS: Vaginal administration of IMN induces increased cervical expression of COX-2, but not of COX-1. This pathway may be of importance in the process of cervical ripening at term.

A longitudinal study of birth control and pregnancy outcome among women in a Swedish population.

The prevalence of contraception and pregnancy outcome in the same women, at 19, 24, and 29 years of age, was assessed in a longitudinal cohort study using a postal questionnaire technique. A one-in-four random sample of all women born in 1962 and resident in the city of Göteborg in 1981, was obtained from the population register (n = 656). Respondents from 1981 were re-assessed in 1986 and 1991. Four hundred thirty women (66%) answered the questionnaire on all three occasions and are included in the analysis. Contraceptive usage was as follows (at 19, 24, and 29 years of age, respectively): oral contraception (OC) 47%/51%/22%; intrauterine device 3%/11%/19%; barrier methods 12%/12%/20%; depot gestagen 0/0.2%/0.4%; no contraception 39%/26%/25%. OCs had been taken at some time by 93%. Reasons give for cessation of OC were: contraception not required 10%/21%/20%; fear of OC 28%/32%/35%; menstrual disorder 17%/13%/14%; weight increase 20%/16%/15%; mental side effects 14%/ 21%/20%; desire to become pregnant 7%/33%/52%. Pregnancy outcome was as follows: Ever pregnant 17%/42%/ 71%; children 5% had 1-2 children/27% had 1-3 children/ 59% had 1-5 children; 12%/25%/30% > or = 1 legal abortion; 3%/8%/15% > or = 1 miscarriage; and > or = 1 ectopic pregnancy 0.2%/1.2%/2.1%. On all three survey occasions, more than 97% of the legal abortions were performed < or = 12 weeks gestation. The complication rate following legal abortion was 7%. The proportion of live births to the total number of pregnancies was 25%, 45%, and 61%. The relationship between method of contraception, history of pregnancy, legal abortion, and smoking habits was analyzed in detail. Despite the availability of effective contraception, the ratio of legal abortions to live births was high. Fear of side effects was the commonest reason for discontinuing OC.

PIP: Contraceptive use patterns and pregnancy outcomes were assessed in a longitudinal cohort study of 656 women (a 1-in-4 random sample) born in 1962 and residing in Goteborg, Sweden, in 1981. Included in the present analysis were the 430 women (66%) who returned all three postal questionnaires (1981 at age 19 years, 1986 at 24 years, and 1991 at 29 years). Contraception had been used at some point by 73% of women at age 19, 94% at age 24, and 97% at age 29. Contraceptive usage, by method, at ages 19, 24, and 29 years, respectively, was as follows: oral contraceptives (OCs) 47%, 51%, and 22%; IUD 3%, 11%, and 19%; barrier methods 12%, 12%, and 20%; depot gestagen 0, 0.2%, and 0.4%; and no method 39%, 26%, and 25%. 93% of respondents had taken OCs at some time in the 10-year study period; the major reasons for discontinuation were fear of side effects, menstrual disorders, weight gain, and mental side effects. Pregnancy outcomes at ages 19, 24, and 29 years, respectively, were as follows: ever pregnant 17%, 42%, and 71%; live births 5%, 27%, and 59%; 1 or more legal abortions 12%, 25%, and 30%; 1 or more spontaneous abortions 3%, 8%, and 15%; and 1 or more ectopic pregnancies 0.2%, 1.2%, and 2.1%. The proportion of live births to the total number of pregnancies was 25% at age 19 years, 45% at age 24 years, and 61% at age 29 years. The shifts in contraceptive use patterns over the 10-year study period reflect both improvements in available contraceptive technologies and changes in women's life situation with increasing age and parity.

Fetal fibronectin in vaginal fluid of women in prolonged pregnancy.

The aim of this study was to determine fetal fibronectin in vaginal fluid of women in prolonged pregnancy, its relationship to a modified Bishop score and its predictiveness of delivery within 3 days. Vaginal samples were collected from 80 women at 42 weeks of gestation for the fetal fibronectin assay. A modified Bishop score was estimated. Fetal fibronectin was determined by a quantitative enzyme immunoassay. The concentration of fetal fibronectin in vaginal fluid was elevated in only 36 of the 80 women. The Bishop score and the time between sampling and delivery were not associated with an elevated fetal fibronectin (> or = 0.05 mg/l). We conclude that fetal fibronectin is not a good indicator of delivery within 3 days. The findings add to our understanding of the complexity of the etiology of postterm labor.

A comparison of contraceptive habits and pregnancy outcome at 19 years of age in two cohorts of Swedish women born 1962 and 1972.

The prevalence of contraception and pregnancy outcome in two representative samples of 19-year-old women resident in the city of Göteborg, born in 1962 (n = 596) and 1972 (n = 641), respectively, was assessed and compared using a postal questionnaire technique. The prevalence of different contraceptive techniques was as follows (62/72): Oral contraception (OC) alone 44%/35%, (p < 0.001); OC + condom 1%/12%, p < 0.001; intrauterine device 4%/1%, p < 0.001; condom only 11%/14%; depot gestagen 0%/0.3%; no contraception 40%/38%. The median duration of OC use was 15 and 14 months, respectively. Fear of OCs was the commonest reason given for cessation of OC in the 62 cohort and that contraception was no longer required in the 72 cohort. The proportion of women who gave the latter explanation for cessation of OC had increased (p < 0.001) from 10% in 1981 to 57% in 1991, indicating that young women in Sweden now tend not to continue with OCs when a relationship ends. Although the prevalence of cigarette smoking was reduced (p < 0.05 in the 72 cohort compared to the 62 cohort), there was still an over-representation of smokers in both cohorts among contraceptive users (p < 0.001) and in women who had been pregnant (p < 0.001) or undergone an abortion (p < 0.001). Pregnancies were reported by 11% of the women from the 62 cohort and by 13% from the 72 cohort. A greater proportion (p < 0.001) of pregnancies terminated in legal abortion in the 72 cohort (61%) compared to the 62 cohort (50%). The medical complication rate following legal abortion was lower (p < 0.05) in the 72 cohort compared to the 62 cohort.

PIP: The prevalence of contraception and pregnancy outcome in two representative samples of 19-year-old women living in Goteborg were assessed via postal questionnaire, then compared. 596 respondents were born in 1962 and 641 in 1972. 44% and 35% of the women born in 1962 and 1972, respectively, used oral contraceptives (OC) only; 1% and 12% used OCs together with condoms; 4% and 1% used IUDs; 11% and 14% used condoms only; 0% and 0.3% used depot gestagen; and 40% and 38% used no contraception. The median duration of OC use was 15 and 14 months, respectively, with fear of OCs being the most common reason for ceasing OC use among the older women. The major reason why younger women stopped using OCs was because they felt that they no longer needed contraception. Younger women in Sweden tend to discontinue OC use when a relationship ends. Cigarette smoking, prior pregnancy, and having had an abortion were significantly associated with contraceptive use. Pregnancies were reported by 11% of the women born in 1962 and 13% of the women born in 1972. 50% of the pregnancies among women of the 1962 cohort were aborted, compared to 61% among women of the 1972 cohort. The medical complication rate following legal abortion was lower among women of the 1972 cohort compared to those of the 1962 cohort.

Cerebrospinal fluid levels of monoamine metabolites. A preliminary study of their relation to menstrual cycle phase, sex steroids, and pituitary hormones in healthy women and in women with premenstrual syndrome.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) were measured in a group of drug-free non-depressed women with premenstrual syndrome (PMS) (late luteal phase dysphoric disorder) (n = 13) and in controls with no premenstrual complaints (n = 13). In six patients and eight controls, CSF samples from both the luteal and the follicular phase were obtained, whereas in the remainder of the subjects, samples from either the follicular phase (patients: 4, controls: 2) or the luteal phase (patients: 3, controls: 3) were taken. The following observations were made: (1) Neither in the follicular phase nor in the luteal phase did the mean concentrations of CSF monoamine metabolites in the PMS group differ from the corresponding values in the control group. (2) Neither in the PMS group nor in the control group did the mean concentrations of monoamine metabolites in CSF samples obtained in the luteal phase differ from the corresponding values obtained in the follicular phase. (3) The intraindividual, intersample variations of CSF HVA and 5-HIAA concentrations were significantly smaller in the PMS group than in the control group. (4) CSF HVA correlated strongly to CSF 5-HIAA in the luteal phase of both patients and controls whereas in the follicular phase, particularly in controls, this correlation was much weaker. (5) In the luteal phase, the CSF HVA/5-HIAA ratio correlated negatively to serum levels of estradiol, progesterone, and testosterone. (6) The CSF HVA/5-HIAA ratio was significantly lower in PMS patients than in controls. (7) A positive correlation between CSF MHPG and serum luteinizing hormone was observed in the follicular phase. (8) A positive correlation between CSF HVA and serum prolactin was observed in the luteal phase. Because the study was comprised of a small number of subjects, the reported findings until replicated should be interpreted with caution.

Serum levels of androgens are higher in women with premenstrual irritability and dysphoria than in controls.

Serum levels of progesterone, total testosterone, free testosterone, androstenedione (A2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone binding globulin (SHBG) were measured in the follicular phase, around ovulation, and in the luteal phase of 11 women with severe premenstrual irritability and dysphoria and in 11 age-matched controls with no premenstrual complaints. Serum levels of free testosterone were significantly higher in the subjects with premenstrual syndrome (PMS) than in the controls in the luteal phase (p < 0.01), the follicular phase (p < 0.05), and around ovulation (p < 0.01). DHEA levels were significantly higher in the PMS subjects, as compared to controls, around ovulation (p < 0.05), while 17-OHP levels were higher in the PMS women in the luteal phase (p < 0.05). With respect to the other steroids measured, as well as SHBG, no differences between PMS subjects and controls were found. These results indicate a possible involvement of androgens in the pathophysiology of premenstrual irritability and dysphoria.

Factors influencing the prevalence and severity of dysmenorrhoea in young women.

Factors influencing the prevalence and severity of dysmenorrhoea were assessed longitudinally in a representative sample of young women born in 1962. The prevalence of dysmenorrhoea was lower (P less than 0.01) at 24 years of age than at 19 years of age. At 24 years of age, 67% of the women still experienced dysmenorrhoea; 10% reported dysmenorrhoea which limited daily activity. The severity of dysmenorrhoea (linear analogue scale) was lower (P less than 0.001) at 24 years of age (3.4, SD 2.8) than at 19 years (4.1, SD 3.2). The prevalence and severity of dysmenorrhoea were reduced (P less than 0.05) in women who were parous in 1986 and nulliparous in 1981, but was unchanged in women who were still nulliparous or women who had had a miscarriage or abortion. Dysmenorrhoea was reduced (P less than 0.001) in oral contraceptive users. The severity of dysmenorrhoea was significantly associated with the duration of menstrual flow, menarcheal age and cigarette smoking. The severity of dysmenorrhoea was not associated with age as an isolated factor, nor with height, weight, length of menstrual cycle or frequency of physical exercise.

Histochemical investigation of cervical intraepithelial neoplasia.

An enzyme histochemical method and histomorphological examination were applied in the cases of 37 patients with cytological atypia. Good agreement was found between the presence of aberrant glucose-6-phosphate dehydrogenase (G-6-PD) activity (metabolic atypia) and histopathologically demonstrable dysplasia. Only three women with metabolic atypia showed a normal histopathological picture. The results suggest that enzyme histochemistry may also be a valuable supplement to histopathology in the diagnosis of cervical neoplastic changes.

Single dose bromocriptine microcapsules in postpartum lactation inhibition.

The clinical efficacy and safety of a single intramuscular injection of Parlodel LA, Pravidel 50 mg, were studied in the prevention of lactation in 10 postpartum women. The overall efficacy at the end of the 28 day observation period was very good in 8 postpartum women and good in 2 women and no rebound lactation occurred. The prolactin plasma levels decreased to normal levels within 4 days in 9 women. Menstrual bleeding occurred in 9 women 4 to 6 weeks after treatment. Laboratory data recorded in this study support that Pravidel is effective in suppressing postpartum lactation.

Progesterone treatment of premenstrual tension--a double blind study.

Fifteen women with moderate to severe premenstrual symptoms, defined and graded according to a recently developed scoring system, took part in a double blind study of the effect of progesterone on premenstrual symptoms. The dosage was 100 mg progesterone twice daily delivered in vaginal pessaries. The women were improved with a statistically significant decrease in their scores by progesterone as well as by placebo treatment. There was no statistically significant difference between the two regimes.

Abnormal dexamethasone suppression test in normal females.

Eighty women taking part in a population study were subjected to a dexamethasone suppression test (DST) intended as a diagnostic aid for melancholia. The women were selected systematically from two age strata, 38 and 50 years. Fifteen subjects (19 per cent) were found to be non-suppressors. High post-dexamethasone serum cortisol concentrations were not the result of elevated concentrations of the main cortisol binder, transcortin. There were no differences between suppressors and non-suppressors as regards depressive symptoms, strain experience, body mass, gynaecological history, drug use, smoking, erythrocyte sedimentation rate, number of leucocytes, activity of serum aminotransferases and gamma-glutamyltransferase, serum iron, bilirubin, ferritin content, serum growth hormone or serum prolactin. However, the nonsuppressors reported a significantly lower (P less than 0.01) orgasmic capacity in a questionnaire inquiry about two weeks before the DST. The outcome of the study indicates that DST as the presently recommended procedure for out-patients has a lower specificity for melancholia than has been reported previously.

An epidemiologic study of young women with dysmenorrhea.

The prevalence of dysmenorrhea was studied in a random sample of 19-year-old women from an urban Swedish population. Dysmenorrhea was reported by 72% of the women. Fifteen percent suffered from dysmenorrhea which limited daily activity and was unimproved by analgesics. Dysmenorrhea occurred significantly (p less than 0.01) more often in women not using oral contraceptives. A significant correlation (p less than 0.01) was found between early menarche and an increased severity of dysmenorrhea. There was a significant correlation (p less than 0.01) between the severity of dysmenorrhea and the amount of menstrual flow. Parous women had significantly (p less than 0.01) less dysmenorrhea than women who had never been pregnant or women who had experienced a legal or spontaneous abortion. Smokers as compared to nonsmokers had significantly (p less than 0.01) less dysmenorrhea. The severity of dysmenorrhea was not affected by height, weight, or regularity of the menstrual cycle. Absenteeism as a result of dysmenorrhea was evaluated.

Bromocriptine and premenstrual tension: a clinical and hormonal study.

Thirty-four patients suffering from the premenstrual syndrome were studied during 5 consecutive menstrual cycles. After a control cycle, bromocriptine and placebo were given during the luteal phase of the cycle in a random, double-blind manner, each patient serving as her own control. Bromocriptine (1.25 mg twice daily) was given for 3 cycles and placebo for 1 cycle. Serum prolactin levels were within normal limits without treatment and were significantly reduced by bromocriptine. Serum progesterone did not change during treatment. Medication considerably improved all the premenstrual symptoms but bromocriptine was not significantly better than placebo. These results do not support the hypothesis that prolactin alone causes premenstrual symptoms.

Does cervix conization increase the risk of complications in subsequent pregnancies?

In a series of 414 patients who underwent cervix conization because of cancer in situ, the risk of complications in subsequent pregnancies was analyzed by studying the outcome of their 923 pregnancies before and after cone biopsy. After conization the incidence of late spontaneous abortion was seven times higher than before. Moreover, 20.5% of pregnancies following cone biopsy required cervix cerclage because of suspected cervical insufficiency, or cesarean section because of a scarred cervix stenosis.

Diagnostic and therapeutic viewpoints on cervical intraepithelial neoplasia. 10-Year follow-up of a conization material.

In 429 women with the diagnosis of cancer in situ (CIS), we found, during a follow-up time of 10 years, a relapse frequency of 5.3%; conization was the primary treatment in 414 cases, in 13 cases hysterectomy and radiotherapy in 2 cases. We found that the mean age was significantly higher (p less than 0.01) when the primary CIS lesion was localized in the cervix (36.8 +/- 10.5) compared to localization only on the portio (31.3 +/- 8.7). The risk of relapse was significantly higher (p less than 0.05) in patients where the primary cone had the lesion localized in the cervix compared to the patients where the primary cone had the lesion localized only to the portio. We found that the localization of PAD relapses appearing later compared to a high degree (about 65%) with the localization of the primary CIS lesion. Vaginal relapse was, generally speaking, twice as common when the primary CIS lesion was localized in the cervix compared to when it was localized on the portio alone. Alternative treatment methods to the conization operation are discussed and an increased individualization of CIS treatment is emphasized particularly with consideration to age and the localization of the CIS lesion.

Hormone profile in premenstrual tension: effects of bromocriptine and diuretics.

Plasma levels of prolactin, FSH, LH, progesterone and 17-beta-oestradiol in twenty women with premenstrual tension were compared with those in twenty controls. The former group was studied also during treatment with bromocriptine. The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase (P less than 0.01), but there was no difference between the PMT and control group in the luteal phase. No differences were found between the controls and the PMT group in FSH,LH, 17-beta-oestradiol and progesterone levels in the luteal phase. Bromocriptine suppressed prolactin concentrations (P less than 0.01), but had no effect on the FSH, LH, 17-B-oestradiol or progesterone levels.