Association of testosterone and antimüllerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy

Sjaarda, Lindsey A.; Kuhr, Daniel L.; Holland, Tiffany L.; Silver, Robert M.; Plowden, Torie C.; Perkins, Neil J.

doi:10.1016/j.fertnstert.2017.11.014

Cited by 11 publications

(11 citation statements)

References 31 publications

(37 reference statements)

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“…Most women with PCOS also exhibit substantially elevated levels of ovarian and serum testosterone (Abbott et al, 2019;Filippou & Homburg, 2017;Rosenfield & Ehrmann, 2016). These results are relevant to fitness variation in that relatively high serum testosterone is associated with reduced fertility and fecundity among females due to anovulation or oligo-ovulation, higher rates of miscarriage, and other causes (Cocksedge et al, 2008;Okon et al, 1998;Sjaarda et al, 2018).…”

Section: Prenatal and Postnatal Testosterone Andmentioning

confidence: 95%

The sexual selection of endometriosis.

Crespi

Dinsdale

2023

Evolutionary Behavioral Sciences

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We propose and evaluate a new theory for helping to explain the evolution of endometriosis risk in humans. By this theory, endometriosis risk evolved in the context of sexual selection by males for high, relatively female-biased expression of sexually dimorphic and female-limited phenotypes associated with low testosterone and high female reproductive fitness. The theory is supported by extensive data, showing that: (a) endometriosis involves higher expression of major female-biasing genes, and lower expression of major male-biasing genes, that orchestrate prenatal sexual differentiation; (b) endometriosis and its correlates are associated with low prenatal and postnatal testosterone, both of which have female-biasing effects on traits; (c) low prenatal and postnatal testosterone, and endometriosis, are associated with relatively female-biased phenotypic expression for a large suite of sexually dimorphic and sex-limited traits; (d) relatively female-biased expression of these traits is commonly associated with higher fertility and fecundity; (e) some traits, including female facial features, vocal pitch, and breast size, fit with all of the predictions of the model, though they have yet to be studied in relation to endometriosis; and (f) traits linked with low prenatal and postnatal testosterone or high estradiol, and traits associated with endometriosis in humans, are preferred by males across multiple species of non-human mammals. Risk and symptoms of endometriosis thus appear to involve and represent, in part, maladaptive extremes of sexually selected female-limited and sexually dimorphic traits.

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Section: Prenatal and Postnatal Testosterone Andmentioning

confidence: 95%

The sexual selection of endometriosis.

Crespi

Dinsdale

2023

Evolutionary Behavioral Sciences

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“…Given the known link between these hormonal factors and PCOS, the most common endocrine disorder in women [ 45 ], our findings are important in understanding potential factors that affect the continuum of PCOS. As women with mild sub-clinical features of PCOS may suffer from ovulatory insufficiency and other factors related to impaired fecundability [ 12 ], our findings also highlight the need to mitigate exposure to this ubiquitous environmental contaminant through modifiable lifestyle changes for women’s reproductive health.…”

Section: Discussionmentioning

confidence: 85%

“…Links between PCOS-phenotypes in otherwise healthy women and manifestation of overt PCOS are not always clear. However, women with a mild PCOS-phenotype who do not meet the diagnostic criteria of PCOS have still been shown to experience reduced fecundability [ 12 ]. As such, investigating associations between cadmium exposure and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Serum testosterone, anti‐Mullerian hormone (AMH), and insulin analyses were previously described in detail 20 . In brief, we first determined total testosterone using a Shimadzu Prominence Liquid Chromatogram (Shimadzu Scientific Instruments, Inc. Columbia, MD) coupled to an AB Sciex 5500 tandem mass spectrometer (AB SCIEX, Framingham, MA).…”

Section: Methodsmentioning

confidence: 99%

“…We assessed anovulation through up to six consecutive study cycles using several data sources as previously described in detail 20 . In brief, all 840 cycles resulting in an hCG‐detected pregnancy were classified as ovulatory.…”

Section: Methodsmentioning

confidence: 99%

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study

Bloom

Perkins

Sjaarda

et al. 2020

Paediatric Perinatal Epid

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Background Obesity, a body mass index (BMI) ≥30 kg/m2, is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility. Objective To characterise the associations between adiposity and anovulation among women menstruating on a regular basis. Methods Women from the EAGeR trial (n = 1200), a randomised controlled trial of low‐dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed‐effects log‐binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti‐Mullerian hormone (AMH), serum lipids, and demographic and life style factors. Results 343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m2 greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors. Conclusions Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.

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Association of testosterone and antimüllerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy

Abstract: NCT00467363.

Cited by 11 publications

References 31 publications

The sexual selection of endometriosis.

The sexual selection of endometriosis.

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

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study

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