Thyroid hormones and female reproduction†

Silva, Juneo Freitas; Ocarino, Natália de Melo; Serákides, Rogéria

doi:10.1093/biolre/ioy115

Cited by 103 publications

(111 citation statements)

References 175 publications

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“…Replacement therapy with thyroid hormones in patients with hypothyroidism causes SHBG, free testosterone, and prolactin to return to normal concentrations [3,9], and sexual dysfunction to resolve [7,11,12]. Taken together, this evidence supports the hypothesis that thyroid hormones may be causally associated with sex hormone concentrations and sexual function in the general population.…”

Section: Introductionsupporting

confidence: 66%

“…Normal thyroid function is important for normal sexual function. Thyroid hormones have direct effects on ovaries, testis and corpora cavernosa via specific nuclear receptors that regulate development and metabolism of these tissues [1][2][3]. Additionally, thyroid hormones regulate bioavailability of sex hormones by increasing the concentrations of hepatic nuclear factor 4α, which in turn increases sex hormone binding globulin (SHBG) transcription and consequently SHBG concentrations [4].…”

Section: Introductionmentioning

confidence: 99%

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Thyroid function, sex hormones and sexual function: a Mendelian randomization study

et al. 2021

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Hypothyroidism and hyperthyroidism are observationally associated with sex hormone concentrations and sexual dysfunction, but causality is unclear. We investigated whether TSH, fT4, hypo-and hyperthyroidism are causally associated with sex hormones and sexual function. We used publicly available summary statistics from genome-wide association studies on TSH and fT4 and hypo-and hyperthyroidism from the ThyroidOmics Consortium (N ≤ 54,288). Outcomes from UK Biobank (women ≤ 194,174/men ≤ 167,020) and ReproGen (women ≤ 252,514) were sex hormones (sex hormone binding globulin [SHBG], testosterone, estradiol, free androgen index [FAI]) and sexual function (ovulatory function in women: duration of menstrual period, age at menarche and menopause, reproductive lifespan, and erectile dysfunction in men). We performed two-sample Mendelian randomization (MR) analyses on summary level, and unweighted genetic risk score (GRS) analysis on individual level data. One SD increase in TSH was associated with a 1.332 nmol/L lower (95% CI: − 0.717,− 1.946; p = 2 × 10-5) SHBG and a 0.103 nmol/l lower (− 0.051,V0.154; p = 9 × 10-5) testosterone in two-sample MR, supported by the GRS approach. Genetic predisposition to hypothyroidism was associated with decreased and genetic predisposition to hyperthyroidism with increased SHBG and testosterone in both approaches. The GRS for fT4 was associated with increased testosterone and estradiol in women only. The GRS for TSH and hypothyroidism were associated with increased and the GRS for hyperthyroidism with decreased FAI in men only. While genetically predicted thyroid function was associated with sex hormones, we found no association with sexual function.

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Section: Introductionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Thyroid function, sex hormones and sexual function: a Mendelian randomization study

et al. 2021

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“…There is a mutual relationship between the thyroid and ovaries, i.e., thyroid hormones affect the female reproductive system, and ovarian hormones affect thyroid function during fertile periods, as well in menopause [74, 75]. Although thyroid diseases are more common in women [76], and hypothyroidism increases with age [77], thyroid hormones during perimenopause are poorly investigated.…”

Section: Discussionmentioning

confidence: 99%

Endocrine profile of the VCD-induced perimenopausal model rat

et al. 2019

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During the transition to menopause, women experience a variety of physical and psychological symptoms that are directly or indirectly linked to changes in hormone secretion. Establishing animal models with intact ovaries is essential for understanding these interactions and finding new therapeutic targets. In this study, we assessed the endocrine profile, as well as the estrous cycle, in the 4-vinylcyclohexene diepoxide (VCD)-induced follicular depletion rat model in 10-day intervals over 1 month to accurately establish the best period for studies of the transition period. Twenty-eight-day-old female rats were injected daily with VCD or oil s.c. for 15 days and euthanized in the diestrus phase approximately 70, 80, 90 and 100 days after the onset of treatment. The percentage of rats showing irregular cycles and the plasma level of FSH increased only in the 100-day VCD group. Plasma anti-Müllerian hormone (AMH) and progesterone were lower in all VCD groups compared to control groups, while estradiol remained unchanged or higher. As in control groups, dihydrotestosterone (DHT) progressively decreased in the 70-90-day VCD groups; however, it was followed by a sharp increase only in the 100-day VCD group. No changes were found in plasma corticosterone, prolactin, thyroid hormones or luteinizing hormone. Based on the estrous cycle and endocrine profile, we conclude that 1) the time window from 70 to 100 days is suitable to study a perimenopause-like state in this model, and 2) regular cycles with low progesterone and AMH and normal FSH can be used as markers of the early/mid-transition period, whereas irregular cycles associated with higher FSH and DHT can be used as markers of the late transition period to estropause.

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“…Elevated THs blood levels exert a negative feedback, inhibiting TRH and TSH release in a diverse set of vertebrates, including human, rat, bird and sheep, among other animals [ 146 ]. Silva and coauthors, in 2018 [ 147 ], reviewed thyroid hormones involvement in female reproduction in humans and other vertebrates, highlighting the thyroid hyperfunction association with androgens and testosterone synthesis, which then are metabolized to estrone and E 2 , respectively, suggesting a positive THs control of aromatizable steroids in the ovary. In contrast, some studies evidenced a negative relationship between hypothyroidism and increased serum concentration of P 4 and PRL, which cause a luteal phase prolongation, as demonstrated by hyperthyroidism induced premature luteolysis in rats (reviewed in [ 147 ]).…”

Section: The Impact Of Vitamin K In Reproductionmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.

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Thyroid hormones and female reproduction†

Cited by 103 publications

References 175 publications

Thyroid function, sex hormones and sexual function: a Mendelian randomization study

Thyroid function, sex hormones and sexual function: a Mendelian randomization study

Endocrine profile of the VCD-induced perimenopausal model rat

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

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