Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study

Abstract Background Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. Methods This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. Results Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. Conclusions Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.

Download Full-text

Plasma volume variation across the menstrual cycle among healthy women of reproductive age: A prospective cohort study

Physiological Reports ◽

10.14814/phy2.14418 ◽

2020 ◽

Vol 8 (8) ◽

Cited By ~ 1

Author(s):

Sixtus Aguree ◽

Hilary J. Bethancourt ◽

Leigh A. Taylor ◽

Asher Y. Rosinger ◽

Alison D. Gernand

Keyword(s):

Cohort Study ◽

Menstrual Cycle ◽

Prospective Cohort Study ◽

Plasma Volume ◽

Prospective Cohort ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Healthy Women ◽

Volume Variation

Download Full-text

Plasma Volume, Hydration and Nutritional Biomarker Concentrations Across the Menstrual Cycle (P24-052-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p24-052-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Sixtus Aguree ◽

Hilary Bethancourt ◽

Leigh Taylor ◽

Asher Yoel Rosinger ◽

Lacy M Alexander ◽

...

Keyword(s):

Menstrual Cycle ◽

Plasma Volume ◽

Plasma Osmolality ◽

Reproductive Age ◽

Magnesium Concentration ◽

Women Of Reproductive Age ◽

Blood Draw ◽

Healthy Women ◽

Markers Of Inflammation ◽

Concentration Changes

Abstract Objectives To examine changes in plasma volume, hydration, and micronutrient concentrations across the menstrual cycle among healthy women of reproductive age. Methods Healthy women aged 18 to 44 years were studied longitudinally across a single menstrual cycle (n = 35). Women made three visits (v1, v2, and v3) to the study center around cycle days 2, 12 and 21 (adjusted for individual cycle length) representing early follicular, late follicular and midluteal phases, respectively. At each visit, blood samples were collected before and after injection of indocyanine green (ICG). ICG in plasma was measured with a spectrophotometer within 2 hours of blood draw, to estimate plasma volume. Urine specific gravity (USG) was measured with a hand-held refractometer; urine and plasma osmolality were measured using freezing point depression osmometry. Serum ferritin was measured by ELISA; serum concentrations for 5 minerals were measured by inductively coupled plasma mass spectrometry. A mixed-effects model was used to examine changes in plasma volume and biomarker concentrations across the menstrual cycle; plasma volume and biomarker associations were tested with Spearman's correlation. Results Participants had a mean (SD) BMI of 21.6 (1.9) kg/m2. Plasma volume showed a non-significant decrease of 122 mL from v1 to v2 (P = 0.165; Table 1) and remained stable from v2 to v3 (P = 0.900). However, plasma osmolality decreased throughout the cycle from v1 to v3 (P < 0.001). Urine osmolality fell slightly from v1 to v2 (P = 0.214) followed by a significant rise from v2 to v3 (P = 0.026) but USG was constant across the cycle. From v1 to v3, serum magnesium concentration declined by 4.5% (P = 0.001); zinc had a similar decline that did not reach statistical significance (P = 0.057). Mean copper, calcium, manganese, ferritin, and hemoglobin concentrations did not change across the cycle (all P > 0.05). Adjusting for markers of inflammation (α1-acid glycoprotein and C-reactive protein) and plasma volume did not affect biomarker concentration changes. Plasma volume was not correlated with nutritional biomarkers at any timepoint (all P > 0.05, Table 2). Conclusions Concentrations of micronutrients were not related to plasma volume. Some hydration and micronutrient biomarkers changed across the menstrual cycle, which could have implications for the timing of measurements in women of reproductive age. Funding Sources The Pennsylvania State University. Supporting Tables, Images and/or Graphs

Download Full-text

The scent of attractiveness: levels of reproductive hormones explain individual differences in women's body odour

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.1520 ◽

2018 ◽

Vol 285 (1886) ◽

pp. 20181520 ◽

Cited By ~ 5

Author(s):

Janek S. Lobmaier ◽

Urs Fischbacher ◽

Urs Wirthmüller ◽

Daria Knoch

Keyword(s):

Individual Differences ◽

Menstrual Cycle ◽

Mate Choice ◽

Reproductive Fitness ◽

Reproductive Hormones ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Hormone Levels ◽

Body Odour ◽

Cortisol Levels

Individuals are thought to have their own distinctive body odour which reportedly plays an important role in mate choice. In the present study we investigated individual differences in body odours of women and examined whether some women generally smell more attractive than others or whether odour preferences are a matter of individual taste. We then explored whether levels of reproductive hormones explain women's body odour attractiveness, to test the idea that body odour attractiveness may act as a chemosensory marker of reproductive fitness. Fifty-seven men rated body odours of 28 healthy, naturally cycling women of reproductive age. We collected all odours at peak fertility to control for menstrual cycle effects on body odour attractiveness. Women's salivary oestradiol, progesterone, testosterone and cortisol levels were assessed at the time of odour collection to test whether hormone levels explain body odour attractiveness. We found that the men highly agreed on how attractive they found women's body odours. Interestingly, women's body odour attractiveness was predicted by their oestradiol and progesterone levels: the higher a woman's levels of oestradiol and the lower her levels of progesterone, the more attractive her body odour was rated. In showing that women's body odour attractiveness is explained by levels of female reproductive hormones, but not by levels of cortisol or testosterone, we provide evidence that body odour acts as a valid cue to potential fertility.

Download Full-text

Transvaginal Echography in Assessing Cyclic Changes in Endocervix in Women of Reproductive Age

Journal of Gynecology & Reproductive Medicine ◽

10.33140/jgrm/01/01/00003 ◽

2017 ◽

Vol 1 (1) ◽

Keyword(s):

Menstrual Cycle ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Group Iii ◽

Healthy Women ◽

Group I ◽

History Of ◽

Group Ii ◽

Cyclic Changes

Objective: To study the echographic semiotics of endocervix in women of reproductive age in different periods of the menstrual cycle in a transvaginal way. Materials and methods: The study included 124 gynecologically healthy women aged 19-45 years. Among the surveyed 14 (11.3 ± 2.8%) had in the history only abortions (group I), 54 (43.6 ± 4.5%) parturition (group II) and in 56 (45.1 ± 4.5 %) of women was not pregnant (group III). 8 (6.4 ± 2.2%) women of I group were aged under of 25 years, 6 (4.8 ± 1.9%)-at the age of 26-35 years. 10 (8.1 ± 2.4%) women of II group were aged under of 25 years, 26 (21.0 ± 3.7%)-at 26-35 years, 18 (14.5 ± 3.2% )-at 36-45 years respectively. 34 (27.4 ± 4.0%) women of III group were aged under of 25 years, 16 (12.9 ± 3.0%)-at 26-35 years and 6 (4.8 ± 1.9% )-at 36-45 years respectively. Results: The thickness of endocervix in women with a lack of pregnancy was 8.9 ± 1.0 mm, which is significantly (p <0.05) more than in other women. Reduced echogenicity of endocervix on the 8-10th days of the menstrual cycle was noted in 73.2 ± 5.9% of women who did not have a pregnancy, in 66.2 ± 5.7% of those who had a history of delivery. The average echogenicity was much more often observed on days 12-14 - in 69,6 ± 6,1% and 72,1 ± 5,4% of women, isoehogenicity on 21-23 days - 76,8 ± 5,6% and In 67.3 ± 5.7%, respectively. Conclusions: The greatest thickness of endocervix is observed on 12-14 days of the cycle in women with the impossibility of pregnancy. On the 8th-10th days of the cycle, the echogenicity of the endocervix is often reduced, on the 12-14 days of the middle, on the 21-23th days - isoechoic.

Download Full-text

Neuropsychological performance and menstrual cycle: a literature review

Trends in Psychiatry and Psychotherapy ◽

10.1590/s2237-60892012000100003 ◽

2012 ◽

Vol 34 (1) ◽

pp. 5-12 ◽

Cited By ~ 7

Author(s):

Eliana Gonçalves V. Souza ◽

Melissa G. Ramos ◽

Cláudia Hara ◽

Bárbara Perdigão Stumpf ◽

Fábio L. Rocha

Keyword(s):

Working Memory ◽

Menstrual Cycle ◽

Cognitive Performance ◽

Motor Skills ◽

Verbal Memory ◽

Luteal Phase ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Healthy Women ◽

Low Performance

Approximately 80% of all women of reproductive age experience psychological and physical changes associated with the premenstrual phase. Cognitive alterations are among the most common complaints. In this context, studies have assessed cognitive performance across the menstrual cycle in healthy women and also in women with premenstrual syndrome (PMS). The main objective of the present study was to review the literature on cognitive function in different phases of the menstrual cycle in women of reproductive age, both healthy and with PMS, in particular premenstrual dysphoric disorder (PMDD). We searched MEDLINE and LILACS databases. A total of 27 studies were selected. The studies used heterogeneous methodologies. Most studies suggested that healthy women show small fluctuations in cognitive performance across the menstrual cycle, with low performance scores in the luteal phase for visuospatial and motor skills, attention and concentration, verbal memory, visual memory, working memory, and reaction time. Among women with PMS or PMDD, low performance scores for visuospatial and motor skills, attention and concentration, verbal memory, working memory, reaction time and impulsivity were also detected in the luteal phase. Symptoms observed in PMS/PMDD patients showed low intensity, but greater when compared with healthy women. Evidence indicates fluctuations in cognitive performance in the different phases of the menstrual cycle in healthy and PMS women, with worse performance for women with PMS/PMDD in the luteal phase. However, methodological limitations prevent us from drawing solid conclusions. Further studies are needed to investigate the impact of these cognitive fluctuations on patients' daily activities.

Download Full-text

Analysis of immunity indices in women of reproductive age with acute uncomplicated pyelonephritis in combination with inflammatory diseases of pelvic organs, depending on the period of the menstrual cycle

HEALTH OF WOMAN ◽

10.15574/hw.2018.128.31 ◽

2018 ◽

pp. 31-38

Author(s):

A.V. Rudenko ◽

◽

S.P. Pasiechnikov ◽

O.V. Romashchenko ◽

P.O. Samchuk ◽

...

Keyword(s):

Menstrual Cycle ◽

Inflammatory Diseases ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Pelvic Organs

Download Full-text

Twice-Daily Subcutaneous Injection of Kisspeptin-54 Does Not Abolish Menstrual Cyclicity in Healthy Female Volunteers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-1069 ◽

2013 ◽

Vol 98 (11) ◽

pp. 4464-4474 ◽

Cited By ~ 19

Author(s):

C. N. Jayasena ◽

A. N. Comninos ◽

G. M. K. Nijher ◽

A. Abbara ◽

A. De Silva ◽

...

Keyword(s):

Menstrual Cycle ◽

Reproductive Function ◽

Reproductive Hormones ◽

Follicular Phase ◽

Hypothalamic Amenorrhea ◽

Healthy Women ◽

Lh Pulsatility ◽

Serum Lh ◽

Healthy Female ◽

Ultrasound Parameters

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim: Our aim was to determine the effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7–14 (n = 5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shorter mean length of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

Download Full-text