Suppression of Plasma Insulin-Like Growth Factor-1 Levels in Healthy, Nulliparous, Young Women Using Low Dose Oral Contraceptives

Jernström, Helena; Olsson, Håkan

doi:10.1159/000292493

Cited by 22 publications

(15 citation statements)

References 8 publications

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“…Whereas physiological doses of oestrogens increase IGF-I levels in young girls, similar doses suppress IGF-I when given as contraceptives in young adult females (19) or as oral replacement therapy in postmenopausal women (20)(21)(22). A similar agedependent effect of oestrogens on IGF-I was recently reported in primates in whom low doses facilitated IGF-I secretion during adolescence, but decreased IGF-I levels once the animal reached adulthood (23).…”

Section: Discussionmentioning

confidence: 55%

Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls

Wajs-Kuto

Beeck²,

Rooman³

et al. 1999

European Journal of Endocrinology

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Objective: Oestrogens are used to inhibit growth in girls with constitutionally tall stature. We studied the changes in different hormones that accompany such therapy. Subjects and methods:In this longitudinal study we examined the levels of total insulin-like growth factor-I (IGF-I), free thyroxine (FT 4 ), thyrotrophin (TSH), testosterone, dehydroepiandrosterone sulphate (DHEA-S), cortisol and prolactin in two groups of girls receiving ethinyloestradiol at a dose of either 0.1 mg daily (group A, n = 22) or 0.2 mg daily (group B, n = 36). Hormonal measurements were performed at start of therapy and after 3, 6 and 12 months. Results: In both groups the levels of IGF-I, testosterone and DHEA-S were reduced while the concentrations of cortisol and prolactin were increased. The pituitary-thyroid axis was not significantly affected by this therapy. The girls receiving 0.2 mg ethinyloestradiol daily had lower IGF-I levels after 12 months of therapy and had higher serum prolactin concentrations than the girls treated with 0.1 mg daily. The reduction in predicted height and the advancement in bone age were similar in both groups. Conclusions: Therapy with pharmacological doses of ethinyloestradiol changes the levels of several hormones including IGF-I, testosterone, DHEA-S, prolactin and cortisol but the role of the respective changes in the inhibition of growth is not clear. The suppression of DHEA-S levels by 40% suggests that the ovaries contribute significantly to the production of this hormone in pubertal girls.

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Section: Discussionmentioning

confidence: 55%

Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls

Wajs-Kuto

Beeck²,

Rooman³

et al. 1999

European Journal of Endocrinology

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“…Most white women have at least one copy of the 19-repeat allele (Jernström et al, 2001b), but the frequency of the 19-repeat allele varies between ethnic groups (Jernström et al, 2001a). Insulin-like growth factor-1 levels decrease in most white OC users compared with white non-users (Jernström and Olsson, 1994). However, the absence of the common 19-repeat allele in the IGF1 gene is associated with high IGF-1 levels during OC use in nulliparous women (Jernström et al, 2001a, b).…”

mentioning

confidence: 99%

Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families

et al. 2005

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BRCA1/2 mutations predispose to early-onset breast cancer, especially after oral contraceptive (OC) use and pregnancy. However, the majority of breast cancers might be due to more prevalent low-penetrance genes, which may also modify the risk in BRCA mutation carriers. The absence of the IGF1 19-repeat allele has been associated with high insulin-like growth factor-1 (IGF-1) levels during OC use. High IGF-1 levels are linked to early-onset breast cancer and larger breast volumes in the general population. The goal of this study was to elucidate the relationships between IGF1 genotype, early-onset breast cancer, breast volume, circulating IGF-1 levels and OC use in a prospective cohort of 258 healthy women p40 years old from high-risk breast cancer families. All women completed a questionnaire including information on reproductive factors and OC use. We measured the height, weight, breast volumes and plasma IGF-1 levels. IGF-1 levels were similar among parous and nulliparous women not using OCs. In all, 13% had no IGF1 19-repeat allele. There was an interaction between IGF1 genotype and OC use on IGF-1 levels (P ¼ 0.026) in nulliparous women and another interaction between IGF1 genotype and parity on breast volume (P ¼ 0.01). Absence of the 19-repeat allele was associated with high IGF-1 levels in nulliparous OC users and with larger breast volumes in parous women and OC users. Incident breast cancers were also more common in women without the 19-repeat allele (log rank P ¼ 0.002). Our results suggest that lack of the IGF1 19-repeat allele modifies IGF-1 levels, breast volume and possibly early-onset breast cancer risk after hormone exposure in young high-risk women.

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“…We stratified the women according to the use of hormonal contraceptives as this changes endogenous hormone levels (Jernström and Olsson, 1994;Jernström et al, , 2005, influences breast volumes in nulliparous women and reduces the CYP1A2 enzyme activity (Rietveld et al, 1984).…”

Section: Resultsmentioning

confidence: 99%

“…Age-adjusted coffee consumption was positively associated with current smoking (Po0.0001), but not with nulliparity or current hormonal contraception. Total breast volumes were positively associated with weight (b ¼ 2.119; Po0.0001), but not with age, current hormonal contraception, nulliparity, current smoking or CYP1A2*1F.We stratified the women according to the use of hormonal contraceptives as this changes endogenous hormone levels (Jernström and Olsson, 1994;Jernström et al, , 2005, influences breast volumes in nulliparous women and reduces the CYP1A2 enzyme activity (Rietveld et al, 1984).Among the non-users, of whom 145 had available breast volumes and CYP1A2*1F genotypes, the association between a moderate-to-high coffee consumption (3 þ cups per day) and breast volume was significantly modified by CYP1A2*1F genotype. Among women carrying at least one C-allele, moderate-to-high consumption was associated with lower standardised breast volumes compared with low consumption (896 vs 749 ml) whereas the standardised volumes were somewhat larger in women with moderate-to-high coffee consumption and the A/A genotype (797 vs 847 ml) (b ¼ À0.303; P interaction ¼ 0.02) (Figure 1).…”

mentioning

confidence: 99%

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

et al. 2008

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As breast volume may be associated with heart cancer risk, we studied the relationship between breast volume, CYP1A2*1F and coffee intake. Among healthy premenopausal non-hormone users, 3 þ cups per day was associated with lower volume only in C-allele carriers (P interaction ¼ 0.02), which is consistent with reports that coffee protects only C-allele carriers against breast cancer. A recent study reported that coffee reduced the risk of breast cancer in BRCA1 carriers with the CYP1A2*1F C-allele but not in those with the CYP1A2*1F A/A genotype (Kotsopoulos et al, 2007). Another study found significantly lower coffee consumption in sporadic breast cancer cases with at least one C-allele compared with the A/A genotype (Bågeman et al, 2008) in spite of the fact that coffee consumption is similar across CYP1A2*1F genotypes in the general population (Cornelis et al, 2006). Some studies (Vatten et al, 1990;Baker et al, 2006;Nkondjock et al, 2006;Ganmaa et al, 2008), but not all (Rosenberg et al, 1985;Vatten et al, 1990;McLaughlin et al, 1992;Stensvold and Jacobsen, 1994;Michels et al, 2002), have reported that moderate-to-high coffee consumption protects against breast cancer, though a mechanism is unknown. None of these studies took CYP1A2*1F into account.Coffee is metabolised by the CYP1A2 enzyme, which also plays a key role in oestrogen metabolism (Le Marchand et al, 1997;Lee et al, 2003). Coffee contains not only caffeine but also phytooestrogens that can interact with and even block the oestrogen receptor (Magee and Rowland, 2004). Women with high coffee intake and the highly inducible CYP1A2*1F A/A genotype (Sachse et al, 1999) have a high 2-hydroxyoestrone (2-OHE1) to 16a-OHE1 ratio (Jernström et al, 2003;Bradlow et al, 2006;Klug et al, 2006). 2-Hydroxyoestrone is a weak oestrogen (Schneider et al, 1984), whereas 16a-OHE1 is procarcinogenic (Telang et al, 1992). In line with this, we found that breast volume in breast cancer patients was significantly higher in women with a lower 2-OHE to 16a-OHE1 ratio . Coffee also affects testosterone and SHBG levels (Ferrini and Barrett-Connor, 1996;Nagata et al, 1998). Although hormonal regulation of breast tissue has been extensively studied, little is known about hormones, genes, diet influence, density, size and diseases of the breast.Mammographic density is a strong risk factor for breast cancer (Boyd et al, 2005), the risk increasing with larger percentage density. The non-inducible CYP1A2*1F C-allele was associated with the percent density in normal-weight postmenopausal women not using hormone therapy (Takata et al, 2007). CYP1A2 enzyme activity has also been associated with density (Hong et al, 2004), and coffee induces CYP1A2 enzyme activity (Djordjevic et al, 2007). There is no direct correlation between breast density and size after adjustment for waist-to-hip ratio and BMI (Beijerinck et al, 1995). However, a larger breast size has been associated with increased breast cancer risk (Kato et al, 1995), especially in lean women (Kusano et al, 2006) or in women wi...

show abstract

Suppression of Plasma Insulin-Like Growth Factor-1 Levels in Healthy, Nulliparous, Young Women Using Low Dose Oral Contraceptives

Cited by 22 publications

References 8 publications

Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls

Hormonal changes during the first year of oestrogen treatment in constitutionally tall girls

Insulin-like growth factor-1 (IGF1) genotype predicts breast volume after pregnancy and hormonal contraception and is associated with circulating IGF-1 levels: implications for risk of early-onset breast cancer in young women from hereditary breast cancer families

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

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