Influence of vitamin D and transforming growth factor β3 serum concentrations, obesity, and family history on the risk for uterine fibroids

Ciebiera, Michał; Włodarczyk, Marta; Słabuszewska-Jóźwiak, Aneta; Nowicka, Grażyna; Jakiel, Grzegorz

doi:10.1016/j.fertnstert.2016.09.007

Cited by 75 publications

(101 citation statements)

References 42 publications

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“…In our study, we obtained also a statistically significant difference in serum TGF-b3 concentrations when comparing patients with UFs who were not treated with UPA with those who were treated with UPA (as well as controls). This confirmed our earlier observations that an elevated TGF-b3 serum level may be a factor that identifies patients at risk for UF development and growth (8).…”

Section: Figuresupporting

confidence: 91%

“…The features that cause high TGF-b3 serum levels may stimulate the development of fibroid-transformed cells, which continue to grow and finally yield clinically relevant tumors (8,11). In our opinion this indicates that UPA is likely to block excessive peripheral production of TGF-b3, which in turn inhibits UF growth (e.g., by modulation of ECM metabolism) (48,50).…”

Section: Figurementioning

confidence: 86%

“…Higher levels of steroid hormones are one of the most important factors inducing the formation and growth of UFs (2,3). Other well-known risk factors include advanced age, increased body mass index (BMI), low parity, family history, and genetics (3,7,8). According to recent studies, these factors may also include reduced hypovitaminosis D (8)(9)(10)(11) and increased transforming growth factor b3 (TGF-b3) serum levels (8,11).…”

mentioning

confidence: 99%

“…Other well-known risk factors include advanced age, increased body mass index (BMI), low parity, family history, and genetics (3,7,8). According to recent studies, these factors may also include reduced hypovitaminosis D (8)(9)(10)(11) and increased transforming growth factor b3 (TGF-b3) serum levels (8,11). These are not all the possible risk factors and further studies are still necessary to determine the other patients who are at an increased risk for developing UFs.…”

mentioning

confidence: 99%

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Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Ciebiera

Włodarczyk

Wrzosek

et al. 2018

Fertility and Sterility

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Section: Figuresupporting

confidence: 91%

Section: Figurementioning

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Ciebiera

Włodarczyk

Wrzosek

et al. 2018

Fertility and Sterility

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“…While the pharmaceutical market is receiving a new form of contraception based only on drospirenone, it may be interesting that apart from the other advantages, it may also have a beneficial effect on patients' vitamin D status [23] and be a suitable OC option in 25(OH)D insufficient patients. According to our latest results, if drospirenone contraception were proven to raise the vitamin D serum level, this could also be a good choice for patients at high risk of uterine fibroids [24,25].…”

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confidence: 99%

Vitamin D serum levels in women using contraception containing drospirenone – a preliminary study

Ciebiera

Włodarczyk²,

Słabuszewska-Jóźwiak

et al. 2019

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Vitamin D is a group of steroid compounds soluble in fats. Vitamin D has powerful, pleiotropic effects all over the human body. It is synthesized in human skin, but can also be found in dietary supplements and fortified foods. Vitamin D receptors (VDR) can be found in many tissues, as well as in the female reproductive tract [1,2]. According to recent reports, it is believed that vitamin D has a beneficial effect on lowering the risk of various diseases, e.g. multiple forms of cancer, diabetes, cardiovascular diseases, metabolic syndrome, multiple sclerosis, inflammatory bowel diseases and uterine fibroids [1][2][3][4][5][6]. Vitamin D regulates cell proliferation and differentiation, inhibits angiogenesis and stimulates apoptosis [1,2,4,5]. Vitamin D levels are mostly measured using serum 25-hydroxyvitamin D (25(OH)D) concentration, which is considered to be the best known marker of vitamin D obtained through both diet and body synthesis. According to Holick, the vitamin D level should be higher than 30 ng/ml [1].Ethinylestradiol (EE2) is a derivative of 17β-estradiol (E2), the major endogenous human estrogen. EE2 is used in many forms of combined oral contraception (COC) and is one of the most commonly used medications for this purpose. Ethinylestradiol is hormonally effective by activating the estrogen receptor and thus exerts its estrogenic effects [7].Drospirenone is a steroidal progestin (of the spironolactone group) used in contraception and hormonal replacement therapy. It is also an aldosterone antagonist with potassium-sparing properties. It is an agonist of the progesterone receptor and an antagonist of the mineralocorticoid and androgen receptors, and hence a progestagen, antimineralocorticoid and antiandrogen. Drospirenone does not present any estrogenic or glucocorticoid or antiglucocorticoid activity. It has a potent antigonadotropic effect at sufficient dosages as a result of progesterone receptor activation. It has been stated that drospirenone has a pharmacological profile that is closely related to that of natural progesterone [8]. Drospirenone is about ten times more potent as an antimineralocorticoid in comparison to spironolactone [8][9][10]. The drospirenone antimineralocorticoid activity promotes sodium excretion and prevents water retention [10].It is believed that contraceptives containing estrogens or estrogens combined with progestins may affect 25(OH)D serum concentrations.

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Family History and Uterine Fibroid Development in Black and African American Women

Langton,

Harmon,

Baird

2024

JAMA Netw Open

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ImportanceUterine fibroids are an understudied condition, with earlier onset in Black than White women. Prior studies of the importance of family history on fibroid development are limited by reliance on hospital-based participant selection, poorly defined measures of family history, and nonsystematic fibroid assessment.ObjectiveTo examine whether family history is a risk factor for fibroid development using prospective ultrasonography data to identify incident fibroids and measure fibroid growth and standardized methods to ascertain family history.Design, Setting, and ParticipantsThis prospective community cohort of Black and African American women from the Detroit, Michigan, area was conducted from January 1, 2010, to December 31, 2018, using 4 standardized ultrasonographic examinations during 5 years to detect fibroids 0.5 cm or larger in diameter and measure fibroid growth. Data analysis was performed between May 2022 and January 2024.ExposuresMaternal fibroid history data were gathered directly from participants’ mothers when possible (1425/1628 [88%]), and 2 exposure variables were created: maternal history of fibroids (diagnosed vs not diagnosed) and age at maternal fibroid diagnosis (20-29, 30-39, or ≥40 years vs not diagnosed).Main Outcomes and MeasuresFibroid incidence was assessed using multivariable Cox proportional hazards regression models; fibroid growth was calculated as change in log-volume per 18 months for fibroids matched at successive ultrasonograms.ResultsA total of 1610 self-identified Black and/or African American women aged 23 to 35 years (mean [SD] age, 29.2 [3.4] years) with no prior clinical diagnosis of fibroids at enrollment were available for analysis. Of 1187 fibroid-free participants at enrollment, 442 (37%) had mothers who were diagnosed with fibroids. Compared with participants without a maternal history of fibroids, those reporting maternal history had an adjusted hazard ratio (AHR) of 1.21 (95% CI, 0.96-1.52). Risk was strongest in those whose mothers were diagnosed at a younger age (20-29 years: AHR, 1.56; 95% CI, 1.11-2.21; 30-39 years: AHR, 1.03; 95% CI, 0.71-1.49; ≥40 years: AHR, 1.11; 95% CI, 0.81-1.52; P = .053 for trend). Fibroid growth rates were higher when mothers were diagnosed with fibroids vs not diagnosed (8.0% increased growth; 95% CI, −1.2% to 18.0%).Conclusions and RelevanceIn this prospective cohort study, results supported maternal history of fibroids as a risk factor for incident fibroids, especially when mothers were diagnosed at a younger age. Maternal history was also associated with increased fibroid growth. Asking patients about their family history of fibroids could encourage patient self-advocacy and inform care.

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Influence of vitamin D and transforming growth factor β3 serum concentrations, obesity, and family history on the risk for uterine fibroids

Cited by 75 publications

References 42 publications

Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Ulipristal acetate decreases transforming growth factor β3 serum and tumor tissue concentrations in patients with uterine fibroids

Vitamin D serum levels in women using contraception containing drospirenone – a preliminary study

Family History and Uterine Fibroid Development in Black and African American Women

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