Age-related differences in features associated with polycystic ovary syndrome in normogonadotrophic oligo-amenorrhoeic infertile women of reproductive years

Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
European Journal of Endocrinology (Impact Factor: 3.69). 01/2002; 145(6):749-55. DOI: 10.1530/eje.0.1450749
Source: PubMed

ABSTRACT To assess the effect of age on clinical, endocrine and sonographic features associated with polycystic ovary syndrome (PCOS) in normogonadotrophic anovulatory infertile women of reproductive years.
Cross-sectional study.
Four hundred and seventy-two oligo-amenorrhoeic infertile patients, presenting with normal FSH and oestradiol concentrations, aged 17-42 years underwent a standardised initial evaluation including: cycle history, body mass index, waist-to-hip ratio and transvaginal ultrasound scanning of ovaries. Fasting blood samples were obtained for extensive endocrine evaluation. Cycle duration, serum levels of gonadotrophins, androgens, oestradiol, insulin, glucose, inhibin B as well as mean number of follicles, ovarian volume and ovarian stroma echogenicity were assessed.
Older women had significantly lower LH and androgen and inhibin B serum levels. Similarly, older women presented with a reduced number of ovarian follicles. Age was inversely correlated with cycle duration (r=-0.112, P=0.02), LH (r=-0.154, P=0.001), testosterone (r=-0.194, P=0.001), androstenedione (r=-0.170, P=0.001), dehydroepiandrosterone (r=-0.157, P=0.001), insulin (r=-0.126, P=0.02), inhibin B (r=-0.118, P=0.03) serum levels and mean follicle number (r=-0.100, P=0.03). A positive correlation was observed between age and glucose to insulin ratio (r=0.138, P=0.009).
Advanced age in normogonadotrophic anovulatory infertile women is associated with lower LH and androgen levels and with a decreased number of ovarian follicles. Although during reproductive years observed differences are relatively small, these age-related changes may affect the observed incidence of PCOS.

Download full-text


Available from: Bart C J M Fauser, Aug 21, 2015
  • Source
    • "Inhibin B is a marker of ovarian antral follicle cohort in PCOS (Bili et al., 2001) and eumenorrheic women (Danforth et al., 1998). Bili et al. (2001) found an age-related reduction in the number of antral follicles and a decrease in inhibin B in 472 PCOS patients and Elting, in 27 women found an age-related reduction in inhibin B increment during FSH-stimulated ovarian reserve testing (Elting et al., 2001). However, Piltonen et al. (2004) found unchanged age-related inhibin B levels in 42 women with PCOS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Subfertility due to chronic anovulation is common in women with polycystic ovary syndrome (PCOS) and is often treated with IVF. Women with PCOS have an increased ovarian follicle and oocyte count, increased ovarian reserve and/or a slower rate of follicle atresia. If so, one would expect women with PCOS to display a delayed reduction in fertility with advancing age as compared with eumenorrheic women. To test this hypothesis, we compared oocyte count and live birth rates among two groups undergoing IVF, 500 women with PCOS and 500 eumenorrheic women with infertility due to tubal factor only. Across the age range of 22-41 years, oocyte count and live birth rates remained stable in women with PCOS. In the eumenorrheic comparison group, these parameters decreased significantly with age. Women with PCOS display sustained fertility with advancing age as compared with infertile eumenorrheic women.
    Human Reproduction 06/2011; 26(9):2499-504. DOI:10.1093/humrep/der214 · 4.59 Impact Factor
  • Source
    • "Earlier studies have shown that the prevalence of PCO decreases with age (Koivunen et al., 1999; Bili et al., 2001). Furthermore, the women with PCOS have been shown to gain regular menstrual cycles when ageing, probably due to age-related follicle loss in the ovaries (Elting et al., 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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.
    Human Reproduction 07/2005; 20(7):1820-6. DOI:10.1093/humrep/deh850 · 4.59 Impact Factor
  • Source
    • "Furthermore, it has been reported previously that cycle irregularities improve with increasing age (Dahlgren et al., 1992; Elting et al., 2000; Bili et al., 2001), possibly associated with a decrease in the follicle cohort size (Elting et al., 2003). Although no information is available regarding the age of menopause in women with WHO 2 anovulation, it has been shown in a cross-sectional study that advanced age is associated with lower LH and androgen levels in this group (Bili et al., 2001), as could be confirmed for the androgens in the current longitudinal study. Both oocyte quantity and quality dictate the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and, when almost no follicles are left, the occurrence of menopause (te Velde et al., 1998). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3-9.0) for WHO 2 patients compared with 1.6 years (range 1.0-7.3) in controls. Serum AMH concentrations were significantly (P < 0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 microg/l, range 0.1-35.8; and AMH2, median = 6.7 microg/l, range 0.0-30.6) compared with controls (AMH1, median = 2.1 microg/l, range 0.1-7.4; and AMH2, median = 1.3 microg/l, range 0.0-5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P < 0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P = 0.03). The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients.
    Human Reproduction 09/2004; 19(9):2036-42. DOI:10.1093/humrep/deh373 · 4.59 Impact Factor
Show more