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.

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.

The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome.

Recent studies indicate that antidepressant drugs with potent serotonin reuptake inhibiting properties are effective in reducing the symptoms of premenstrual syndrome (PMS). In order to elucidate whether all antidepressant drugs are equally effective in the treatment of PMS or whether potent serotonin reuptake inhibition is a prerequisite for reducing premenstrual complaints, women suffering from severe PMS were treated daily for three menstrual cycles with a selective serotonin reuptake inhibitor, paroxetine (n = 22), or with a selective noradrenaline reuptake inhibitor, maprotiline (n = 21); in addition, a placebo group was included (n = 22). Six symptoms (irritability, depressed mood, tension/anxiety, increased appetite/craving for carbohydrates, bloating, and breast tenderness) were rated by the participants daily throughout the study. With respect to all outcome measurements, the symptom reduction obtained with paroxetine was significantly superior to that obtained with placebo; with respect to irritability, increased appetite/carbohydrate craving, bloating, and breast tenderness, as well as global self-rating, paroxetine was significantly superior also to maprotiline. The clear-cut superiority of paroxetine over maprotiline indicates that not all antidepressant drugs are equally effective in the treatment of PMS; rather, like panic disorder and obsessive compulsive disorder, but in contrast to depression, PMS apparently responds better to serotonin reuptake inhibitors than to antidepressants with a noradrenergic profile.

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.

Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.

RATIONALE: It is well established that serotonin reuptake inhibitors (SRIs) are effective for the treatment of premenstrual dysphoria (PMD), but the receptor subtype(s) mediating this effect of serotonin have yet not been identified. OBJECTIVE: In this trial, the possible efficacy of buspirone, a partial 5HT1A receptor agonist, and nefazodone, a combined SRI and 5HT2 receptor antagonist, was evaluated in women with PMD. METHODS: After a three-menstrual-cycle screening phase, patients were randomised to buspirone (n=19), nefazodone (n=22) or placebo (n=22). During the first two treatment cycles, patients were taking the drug during the luteal phase only (mean +/- SD daily dose of buspirone: 21 +/- 6 mg; nefazodone: 228 +/- 54 mg). During the subsequent two cycles, the medication was taken each day of the menstrual cycle (mean daily dose of buspirone: 27 +/- 10 mg; nefazodone: 304 +/- 95 mg). RESULTS: With respect to self-rated global improvement, buspirone (P<0.001) but not nefazodone was significantly superior to placebo. While buspirone appeared to reduce self-rated irritability (visual analogue scale) more effectively than placebo, other self-rated symptoms did not differ markedly between the groups. The side-effects were mild, and sexual dysfunction was not significantly more common in patients given buspirone or nefazodone than in those given placebo. CONCLUSION: It is suggested that buspirone is mildly effective for premenstrual irritability. In patients experiencing sexual dysfunction when treated with an SRI, buspirone may be a useful alternative.

A naturalistic study of paroxetine in premenstrual syndrome: efficacy and side-effects during ten cycles of treatment.

Eighteen women with severe premenstrual syndrome (PMS) (premenstrual dysphoric disorder, PMDD) were treated openly with paroxetine for 10 consecutive menstrual cycles. Dosage was flexible (5-30 mg/day); also, the patients were free to chose between continuous medication and medication in the luteal phase only. The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period. Sedation, dry mouth, and nausea were common side-effects but declined during the course of the trial; in contrast, reduced libido and anorgasmia, which were reported by almost 50% of the participants, were not improved with time. The results indicate that the beneficial effects as well as the sexual side-effects of serotonin reuptake inhibitors persist unchanged for at least 10 consecutive cycles of treatment.

Bromocriptine and premenstrual symptoms: a survey of double blind trials.

This is a survey of 14 placebo-controlled studies regarding the treatment of premenstrual symptoms with bromocriptine. There is no substantial support that bromocriptine is an effective drug in the premenstrual syndrome as an entity. Symptoms such as irritability, depression, and anxiety were not significantly improved during treatment with bromocriptine compared to placebo treatment. Bromocriptine appears to be the treatment of choice in premenstrual mastodynia if the dosage of bromocriptine is at least 5 mg daily. Bromocriptine may therefore have a place in selected cases of the premenstrual syndrome with associated mastodynia.

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.

Contraception and pregnancy among young women in an urban Swedish population.

The reproductive history and use of contraception in a representative sample of 19-year-old women from the city of Göteborg is reported. Oral contraceptives (OC) were taken by 47%, 4% had an intrauterine device and 12% used a barrier method while 37% practiced no form of contraception. The type of OC used and reasons for discontinuation are presented. The duration of OC use was one year or less for 46% of the women and exceeded 3 years in only 10%. Major causes of discontinued OC were the result of side effects attributed by the woman to OC, or a fear of OC. There were 93 pregnancies reported in the population sample, resulting in the birth of 34 infants. Pregnancy was terminated by legal abortion in 51% of the reported pregnancies. The ready availability of a return visit to discuss possible side effects and fears resulting from the chosen method of contraception may improve continuity, thus reducing the number of legal abortions.

A longitudinal study of contraception and pregnancy outcome in a representative sample of young Swedish women.

The prevalence of contraception and pregnancy history in the same women, aged 19 and 24 years, was assessed in a longitudinal cohort study by means of a postal questionnaire. A one-in-four random sample of all the women born 1962, resident in the city of Göteborg in 1981, was obtained from the population register (n = 656). The response rate was 91%. Respondents from 1981 were re-assessed in 1986 (response rate: 83%). The respondents from 1986 (n = 488) represent 74% of the original sample from 1981. Contraceptive usage in the same women aged 19 and 24 years (in brackets) was as follows: Oral contraception (OC) 47% (51%); intrauterine device 3% (11%), p less than 0.01; barrier methods 11% (11%); depot gestagen 0 (0.2%); no contraception 39% (26%), p less than 0.05. OCs were being taken or had been taken by 89%. Reasons given for cessation of OC were as follows: Contraception not required 10% (15%); fear of OC 26% (29%); menstrual disorder 17% (14%); weight increase 18% (10%), p less than 0.05; mental side effects 15% (9%); desire to become pregnant 7% (17%), p less than 0.01. Pregnancies (n = 362) were reported by 194 (43%) of the women. 44% of the pregnancies terminated in legal abortion. The medical complication rate following legal abortion was 15%. Thus, 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: The prevalence of contraception and pregnancy history in the same women ages 19-24 was assessed in a longitudinal cohort study by means of a postal questionnaire. A 1-in-4 random sample of all women born in 1962, resident in the city of Goteborg in 1981, was obtained from the population register (n=656). The response rate was 91%. Respondents from 1981 were reassessed in 1986 (response rate=83%). Respondents from 1986 (n=488) represent 74% of the original sample from 1981. Contraceptive usage in the same women ages 19-24 (in brackets) was as follows: oral contraceptives (OCs) 47% (51%): IUD 3% (11%), p0.01; barrier methods 11% (11%), depot gestagen 0 (0.2%); no contraception 39% (26%), p0.05. OCs were taken or had been taken by 89%. Reasons given for the cessation of OCs were the following: contraception not required 10% (15%), fear of OCs 26% (29%), menstrual disorders 17% (14%), weight increases 18% (10%), p0.05; emotional side effects 15% (9%), desire to become pregnant 7% (17%), p0.01. Pregnancies (n=362) were reported by 194 (43%) of the women. 44% were terminated in legal abortion and the medical complication rate following legal abortion was 15%. Thus, despite the availability of effective contraception, the ratio of legal abortions to livebirths was high. Fear of side effects was the most common reason for discontinuing OC use.

The influence of different combined oral contraceptives on the prevalence and severity of dysmenorrhea.

The influence of different oral contraceptives (OC) on the prevalence and severity of dysmenorrhea was investigated longitudinally (from age 19 to 24 years) in a representative sample of young women from an urban Swedish population. The women were grouped according to the type of OC used at the time of assessment: monophasic OC with low gestagen activity; progestogen-dominated monophasic OC; triphasic OC; neither OC nor an intrauterine device (IUD). At the age of 19 years, the severity of dysmenorrhea was lower in users of monophasic OCs with low gestagen activity (p less than 0.05) and users of progestogen-dominated monophasic OCs (p less than 0.001) compared to women who used neither OC nor an IUD. At 24 years of age, the severity of dysmenorrhea was lower in users of monophasic OCs with low gestagen activity (p less than 0.001), users of progestogen-dominated monophasic OCs (p less than 0.001) and users of triphasic OCs (p less than 0.001), compared to women who used neither OC nor an IUD. The severity of dysmenorrhea in women who did not use an OC or IUD when 19 years old was reduced in the same women who used OCs when 24 years old, compared (p less than 0.001) to women who still used neither an OC nor an IUD. There were no significant differences in the prevalence and severity of dysmenorrhea between the users of monophasic OCs, irrespective of progestagen activity, and users of triphasic preparations.

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.

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.

The effect of various oral contraceptive combinations on premenstrual symptoms.

The influence of different oral contraceptives on premenstrual complaints was examined in 191 randomly selected women from an urban population. Premenstrual depression and abdominal swelling was significantly more common in women taking oral contraceptives containing the progestogen component lynestrenol than those containing norgestrel. The reason for this difference is discussed. A deficiency of pyridoxine which affects tryptophan metabolism can explain the difference in premenstrual depression. However, it should be emphasized that the system which controls neuro-endocrine balance is extremely complicated and does not at the present time permit any definite conclusions regarding the influence of oral contraceptives on mental complaints.

PIP: The frequency and degree of severity of defined premenstrual symptoms in a group of women treated with different oral contraceptives (OCs) was studied through mail questionnaires completed by 913 of 1083 women aged 18-46 randomly selected from the Gothenburg population register. The 6 symptoms studied, irritability, depression, anxiety, swelling of fingers and legs, abdominal swelling, and breast swelling, were defined according to the Comprehensive Psychopathological Rating Scale (CPRS). The Pitman Permutation Test was used in the statistical analysis. Of the 191 women who reported taking OCs, 116 (57.4%) used preparations containing norgestrel, 57 (23.2%) used preparations containing lynestrenol, and 7.9% used preparations containing norethisterone. The premenstrual symptoms of irritability and abdominal swelling had the highest symptom scores irrespective of the OC taken. There was no statistical difference between estrogen and progestogen dominated OCs in the severity of the individual symptoms. Women taking lynestrenol were significantly more depressed and had a greater degree of abdominal swelling than women taking norgestrel, but there was no difference between them in the severity of the other symptoms.

Ibuprofen and naproxen-sodium in the treatment of primary dysmenorrhea: a double-blind cross-over study.

The efficacy of ibuprofen and naproxen-sodium for the treatment of primary dysmenorrhea was evaluated in a double-blind cross-over study in 57 otherwise healthy women. The severity of pain reported by the patients was significantly (P less than 0.01) reduced during treatment with both ibuprofen and naproxen-sodium compared to the severity of pain before the first dose. The mean pain relief during treatment with ibuprofen was significantly (P less than 0.05) greater than during treatment with naproxen-sodium in the dosages indicated.

Pre-eclampsia, hypertension and the premenstrual tension syndrome.

A total of 261 of 17,000 pregnancies were complicated by pre-eclampsia/hypertension in pregnancy. Seven to twelve years later 237 were available for follow-up together with 33 women, who had a normotensive pregnancy in 1969-1973. The association between pre-eclampsia/hypertension and the premenstrual tension syndrome has been studied. Women with present hypertension complained significantly (P less than 0.05) more of premenstrual sadness than the normotensive women. However, women with previous pre-eclampsia/hypertension in pregnancy did not have more premenstrual symptoms than women in general, on the contrary, women with a history of severe pre-eclampsia had less symptoms.

[Serotonin uptake inhibitors provide rapid relief from premenstrual dysphoria. New findings shed light on how serotonin modulates sex hormone-related behavior]. / Serotoninupptagshämmare ger snabb lindring vid premenstruell dysfori. Rön som belyser hur könshormonrelaterat beteende moduleras av serotonin.

Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome, afflicting 5-10% of all women. The cardinal symptom--surfacing between ovulation and menstruation, and disappearing within a few days after the onset of the bleeding--is irritability. Serotonin reuptake inhibitors (SRIs), but not non-serotonergic antidepressants, reduce the symptoms of PMD very effectively. Since the, onset of action of SRIs is rapid when used for PMD, medication may be restricted to the luteal phase. The finding that SRIs are effective for PMD lends support for the hypothesis that a major role for brain serotonin is to modulate sex steroid-driven behavior.

Prediction of later hypertension following a hypertensive pregnancy.

The aim of the present study was to identify factors predicting later hypertension following a hypertensive pregnancy. In the years 1969-1973, 261 out of a total of 17 000 pregnancies were complicated by pre-eclampsia or hypertension in pregnancy. In a follow-up study seven to 12 years later, 238 (91.2%) of these women were investigated. It was discovered that 26.4% of the women had hypertension and 10.1% had borderline hypertension compared with 2 and 6.5% respectively in a group of matched control subjects. A stepwise regression analysis was performed in order to evaluate the association between nine different variables and blood pressure at follow-up. We found that systolic blood pressure in early pregnancy was the single most important factor predicting systolic blood pressure at follow-up (r2 = 0.28). When highest recorded blood pressure before delivery and age were entered into the statistical model, r2 was increased to 0.35 (P less than 0.0001). Unlike previous studies, parity and proteinuria did not add to the predictive power of the analysis. Late hypertension was found in more than 25% of women seven to 12 years after a hypertensive pregnancy. The most important factor associated with later hypertension was blood pressure before pregnancy.