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Riitta Koivunen

Publications and source records attributed to Riitta Koivunen.

10 recordsLinked to original sources

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication.

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.

Adolescent↗

Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function in women with epilepsy.

PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously. METHODS: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.

Adolescent↗

Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome.

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.

Adult↗

Associations between two single nucleotide polymorphisms in the adiponectin gene and polycystic ovary syndrome.

In the present study we determined whether genetic variability in the gene encoding adiponectin is associated with polycystic ovary syndrome (PCOS). Altogether 143 Caucasian women with PCOS and 245 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) in exon 2 and intron 2 in the adiponectin gene. Single-point analysis was expanded to pair-of-loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization algorithm. A significantly different allele distribution in intron 2 SNP was observed between the groups, with the T allele being significantly reduced in the PCOS group (25.9%) compared with the control group (32.7%) ( p = 0.047), at an odds ratio of 0.72 (95% confidence interval 0.52-0.99). Otherwise, the allele and genotype distributions in either SNP were not statistically different between the groups. In haplotype estimation analysis, there was a lower frequency of the haplotype T-T in the PCOS group (25.9%) than in the control group (32.7%) ( p = 0.058). We conclude that polymorphisms of the adiponectin gene may be implicated in individual susceptibility to PCOS.

Adiponectin↗

Ovarian age-related responsiveness to human chorionic gonadotropin in women with polycystic ovary syndrome.

Ovarian steroid secretion capacity starts to decline as early as around the age of 30 yr. Whether an age-related decrease in androgen secretion, as in normal women, also occurs in women with polycystic ovary syndrome (PCOS) and whether the enhanced androgen production in PCOS remains throughout the fertile period of life are not known. The aim of this study was to determine the age-related serum basal and gonadotropin-stimulated androgen levels in women with PCOS and to compare the results with those obtained from our previous study in healthy women with normal ovaries. Human chorionic gonadotropin (hCG) stimulation tests were carried out among 42 women with PCOS (age, 16-44 yr; body mass index, 31.02 +/- 1.1 kg/m(2)). An im injection of 5000 IU hCG was given 2-4 d after spontaneous or progestin-induced menstrual bleeding, and blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone, androstenedione (A), testosterone (T), and estradiol assays were collected at 0, 24, 48, and 96 h. In women with PCOS, basal serum T and A levels were about 50% higher than in healthy women. The responses of A and T to hCG [area under the curve (AUC), 96 h)] were significantly higher in women with PCOS than in normal women [A, 1183.6 +/- 60 (+/-se) vs. 814.4 +/- 39 (P <or= 0.001); T, 192.9 +/- 12 vs. 117.4 +/- 6; P <or= 0.001]. In PCOS women, the hCG-stimulated A levels correlated negatively with age (AUC of A: r = -0.044; P = 0.004), and a similar trend was also observed in AUC T levels (AUC of T: r = -0.125, P = 0.425). Despite the higher androgen secretion capacity in PCOS, the basal and hCG-stimulated serum estradiol levels were similar to those observed in normal women. LH correlated positively with age, but basal FSH and inhibin B levels remained unchanged. In conclusion, in PCOS basal serum levels of androgens and ovarian androgen secretion capacity are markedly increased and remain high throughout the reproductive years, although the decreasing ovarian capacity to release androgens in response to hCG stimulation seen in healthy women also occurs in PCOS.

Adolescent↗

Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study.

Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. Metformin did not have any effect on glucose tolerance or insulin sensitivity, but fasting insulin concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P = 0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P = 0.01), and hepatic insulin clearance increased during the treatment. Furthermore, metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2 nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any significant effect on glucose tolerance, serum insulin levels, or insulin sensitivity, but it increased slightly the body mass index (P = 0.09) and significantly serum leptin concentrations (P < 0.001) and decreased serum testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.

Adult↗

Ovarian age-related responsiveness to human chorionic gonadotropin.

Human fertility starts to decline after the age of 30 yr, but the change in ovarian endocrine function, i.e. estrogen biosynthesis, with advancing age is not well understood. To study age-related changes in androgen secretion and ovarian capacity to synthesize/release androgens in response to human chorionic gonadotropin (hCG) stimulation, 44 healthy women (aged 20-44 yr) were investigated. Just before a single im injection of 5000 IU hCG, blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), and estradiol (E(2)) assays were collected. Further samples were taken at 24, 48, 72, and 96 h. The responses of 17-OHP, A, and T to hCG, i.e. areas under the curves (AUC; 96 h), correlated negatively with age (17-OHP: r = -0.427; P = 0.004; A: r = -0.266; P = 0.081; T: r = -0.354; P = 0.018). Despite a decreasing capacity of the ovaries to secrete these estrogen precursors, the basal serum levels of E(2) remained unchanged. This may be due to the rise in serum FSH levels observed as early as after the age of 25 yr [</=25 yr: FSH, 5.1 +/- 0.5 (+/-SE) U/liter; >25 yr: FSH, 7.7 +/- 0.9 U/liter; P = 0.01]. No correlation was found between age and serum inhibin B levels. In conclusion, ovarian androgen secretion capacity starts to decline as early as before the age of 30 yr. Despite that, circulating E(2) levels remain normal for years, possibly due to compensatory mechanisms, reflected by the gradual rise in serum FSH levels.

17-alpha-Hydroxyprogesterone↗

Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study.

OBJECTIVE: Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today. The results of studies on selective serotonin reuptake inhibitors (SSRIs) are promising, but long-term results do not exist. The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women. DESIGN: One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months. They were randomized into three groups receiving placebo, fluoxetine, or citalopram. The initial dose was 10 mg of both fluoxetine and citalopram, and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit. The main outcome measures were hot flushes and Kupperman index. The RAND-36 Quality of Life questionnaire, Beck's Depression Scale, and the McCoy Female Sexuality Questionnaire were used at every control visit. RESULTS: There were no statistically significant differences between the groups in respect to number of hot flushes, Kupperman index, or Beck's Depression Scale, although there was a tendency in all these parameters in favor of SSRIs versus placebo. Insomnia improved significantly in the citalopram group versus placebo. Discontinuation rates at nine months were 40% in the placebo group, 34% in the fluoxetine group and 34% in the citalopram group. CONCLUSIONS: Compared with placebo, citalopram and fluoxetine have little effect on hot flushes and cannot therefore be recommended for the treatment of menopausal symptoms, if vasomotor symptoms are the main complaint. Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation.

Aged↗