Urinary cadmium concentrations and risk of primary ovarian insufficiency in women: a case-control study.

Cadmium, a toxic heavy metal that occurs in the environment in large quantities through human activities, has been shown to have adverse effects on female reproductive health. However, the association between cadmium exposure and primary ovarian insufficiency (POI), one of the most prevalent ovarian diseases in women, has not been examined yet. This case-control study involving 169 POI cases and 209 healthy controls was conducted in Zhejiang Province, China. The urinary concentrations of cadmium were determined by inductively coupled plasma mass spectrometry (ICP-MS). In addition, serum levels of reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH) and estradiol, were measured. The median concentration of urinary cadmium in POI cases (0.43 µg/L, 0.58 µg/g for creatinine adjustment) was significantly higher than that of controls (0.29 µg/L, 0.43 µg/g for creatinine adjustment). The results of binary logistic regression models showed that the concentrations of urinary cadmium were positively significantly correlated with the odds ratio (ORs) of POI before the adjustment of confounders. After the adjustment, a significantly positive association was still present between the increased concentrations of cadmium and the ORs of POI (2.50, 95% CIs: 1.34-4.65 for the third tertile, p for trend = 0.001). The serum levels of FSH and LH were positively associated with urinary cadmium, while AMH and estradiol levels were inversely correlated. To the best of our knowledge, this is the first reported positive association of cadmium exposure with the risk of POI in women.

Clinical utility of urinary gonadotrophins in hypergonadotrophic states as Turner syndrome.

Background Girls with Turner syndrome (TS) are at an increased risk of primary ovarian insufficiency (POI). Good correlation between serum and urinary gonadotrophins exists in children assessed for disorders of puberty, but there is little evidence of their reliability in hypergonadotropic states. Objectives To determine whether there was a correlation between serum and urinary Luteinising Hormone (uLH) and Follicle-Stimulating Hormone (uFSH) in hypergonadotrophic states, and whether uFSH could suggest an ovarian failure in TS as Anti-Mullerian Hormone (AMH). Patients and Methods Retrospective cohort study of 37 TS girls attending the paediatric TS clinic in Glasgow between February 2015 and January 2019, in whom 96 non-timed spot urine samples were available with a median age at time of sample of 12.89 years (3.07-20.2 years). uLH and uFSH were measured by chemiluminescent microparticle immunoassay. Simultaneous serum gonadotrophins and AMH were available in 30 and 26 girls, respectively. AMH <4 pmol/L was considered indicative of ovarian failure. Results A strong correlation was found between serum LH and uLH (r 0.860, P<0.001) and serum FSH and uFSH (r 0.905, p<0.001). Among patients≥10 years not on oestrogen replacement, ROC curve identified uFSH as a reasonable marker for AMH<4 pmol/L uFSH of >10.85 U/L indicates an AMH <4 pmol/L with 75% sensitivity and 100 % specificity (AUC 0.875)with similar ability as serum FSH (AUC 0.906). Conclusion uLH and uFSH are non-invasive, useful and reliable markers of ovarian activity in hypergonadotropic states as TS. uFSH could provide an alternative to AMH (in centres which are limited by availability or cost) in revealing ovarian failure and requirement for oestrogen replacement in pubertal induction.

Urinary levels of phthalate metabolites in women associated with risk of premature ovarian failure and reproductive hormones.

Phthalates, a class of high production-volume chemicals widely used as plasticizers, have been shown to impair ovarian functions in female animals, but epidemiological evidence is very limited. In this case-control study, the associations between phthalate exposure and premature ovarian failure (POF) in women were assessed. A total of 173 POF cases and 246 control women were recruited in Zhejiang, China. The urinary concentrations of 8 phthalate metabolites and the serum levels of ovary-related hormones were determined. Mono-isobutyl phthalate (MiBP) was the metabolite with the highest median concentration of 27.23 µg/g of creatinine in the whole group. Compared with the lowest quartile, higher urinary concentrations of MiBP were significantly associated with increased odds of POF (OR = 1.38, 95% CI: 0.73-2.61 for the fourth quartile; p for trend = 0.01). The estradiol/FSH ratio, a marker of ovarian function, in control women was significantly negatively associated with the urinary concentrations of most tested phthalate metabolites. Our results suggest that exposure to some phthalates may impair ovarian function and increase the odds of POF in women.

Enhanced hypothalamic-pituitary sensitivity to estrogen in premenopausal women with diminished ovarian reserve compared with older perimenopausal controls.

OBJECTIVE: We have previously characterized the reproductive hormone profile in infertile women with diminished ovarian reserve (DOR) as being distinct from that seen in age-comparable healthy controls. Hypothesizing that DOR reflects accelerated reproductive aging, we herein compare urinary reproductive hormone dynamics between young women with DOR and a population of chronologically older perimenopausal controls. METHODS: In this prospective observational study, urinary levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) and metabolites of estrogen (estrone conjugate) and progesterone were assessed in daily morning urine samples collected in a spontaneous menstrual cycle in 8 infertile premenopausal women with DOR and in 11 perimenopausal controls. Areas under the curves were calculated for the respective measured hormones, and comparisons were made using the Mann-Whitney U test. RESULTS: Urinary estrone conjugate levels were significantly attenuated in premenopausal women with DOR compared with the older perimenopausal cohort. Despite the relatively lower estrogen, a significantly more pronounced luteinizing hormone surge was evident in the younger population. Early follicle-stimulating hormone was lower in women with DOR, but luteal urinary progesterone excretion was comparable in the two groups. CONCLUSIONS: Our data suggest distinctions in functioning of the central (hypothalamic-pituitary) and peripheral (ovarian) components of the hypothalamic-pituitary-ovarian axis in premenopausal women with DOR compared with chronologically older perimenopausal controls. Increased hypothalamic-pituitary sensitivity to estrogen positive feedback is suggested in premenopausal women with DOR. Our observations identify DOR as a distinct entity in the paradigm of reproductive senescence.

Characterizing the reproductive hormone milieu in infertile women with diminished ovarian reserve.

OBJECTIVE: To elucidate the reproductive hormone profiles in association with a diagnosis of diminished ovarian reserve (DOR). DESIGN: Prospective observational study. SETTING: Academic tertiary care infertility practice. PATIENT(S): Eight regularly cycling infertile women diagnosed with DOR as the underlying contributor to infertility and 14 age-comparable healthy controls. INTERVENTION(S): Daily morning urine voids were collected during one menstrual cycle. MAIN OUTCOME MEASURE(S): Urinary excretion of gonadotropins (FSH, LH) and metabolites of estrogen (E; estrone conjugate) and P (pregnanediol 3 glucoronide) during an entire menstrual cycle in women with DOR and healthy controls. RESULT(S): Women with DOR demonstrated significantly higher urinary FSH levels in the early follicular phase, exaggerated amplitudes, significantly protracted durations of LH, concomitant FSH surges, and significantly impaired luteal phase urinary excretions of estrone conjugate and pregnanediol 3 glucoronide compared with the controls. CONCLUSION(S): Women with DOR demonstrate reproductive hormone profiles that are distinct from age-comparable controls, share similarities with profiles previously described during menopause transition, as well as exhibit unique features not previously recognized in the context of reproductive aging.

[Evaluation of ovarian follicular reserve]. / Evaluation de la réserve folliculaire ovarienne.

Qualitative and/or quantitative impairment of the ovarian follicular reserve is frequently observed in women consulting for infertility, whatever their age and the cause of infertility. The diagnosis of incipient ovarian failure can not be established on clinical signs. It is established by measuring serum FSH levels in the early phase of a spontaneous cycle and/or by measuring serum FSH level on day 10 of a cycle after administration of clomiphene citrate (100 mg/day) from day 5 to day 9.