Search PubMed⌕ Search

Biomedical subjects

Laure Morin-Papunen

Publications and source records attributed to Laure Morin-Papunen.

8 recordsLinked to original sources
PubMed2026

Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Humans↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2003

A practice guideline for treatment of eating disorders in children and adolescents.

Eating disorders are diseases of both the body and the psyche. Early treatment focuses on restoration of nutritional status and somatic health, including psycho-educational counselling and support offered to the patient and his/her family. Diagnosis and treatment require a multidisciplinary approach. Psychological factors related to the condition should be assessed. The most severe weight loss should be reversed before psychotherapeutic treatment. Nutritional counselling is recommended, and the benefits of individual and/or family therapy are considered in accordance with the patient's age, development, symptomatology and comorbid psychiatric disorders. Medication is useful in the treatment of bulimia nervosa and certain comorbid symptoms of anorexia nervosa. Early admission to treatment and active therapy are associated with a more favourable prognosis.

Adolescent↗
PubMed2003

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↗
PubMed2003

Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome.

Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) </= 25 kg/m(2)] and 32 obese women (BMI >/==" BORDER="0"> 27 kg/m(2)) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 micro g)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 +/- 0.53 (SE) vs. 1.31 +/- 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 +/- 0.68 mg/liter to 4.58 +/- 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.

Adult↗