Effect of low doses of estradiol on 6-month growth rates and predicted height in patients with Turner syndrome

Ross, Judith L.; Long, Lauren; Skerda, Marilyn; Cassorla, Fernando; Kurtz, David; Loriaux, D. Lynn; Cutler, Gordon B.

doi:10.1016/s0022-3476(86)80274-8

Cited by 88 publications

(39 citation statements)

References 15 publications

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“…Most of our knowledge of the effect of low dose estrogen on epiphyseal growth comes from clinical studies in girls with Turner syndrome, in which it has been suggested that estrogen has a biphasic doseresponse relationship for epiphyseal growth, with stimulation at low levels and a reduced effect, or even inhibition, at high levels (24)(25)(26). In Turner girls, a dose of 100 ng/kg/day ethinylestradiol administered orally for 5 weeks resulted in a significantly increased growth velocity, whereas higher doses did not increase the growth rate.…”

Section: Biological Effects Of Low Doses Of Sex Steroidsmentioning

confidence: 99%

Exposure to exogenous estrogens in food: possible impact on human development and health

1999

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There has been increasing concern about the impact of environmental compounds with hormone-like action on human development and reproductive health over the past decades. An alternative but neglected source of hormone action that may be considered in this connection is hormone residues in meat from husbandry animals treated with sex steroid hormones for growth promotion. Treatment of cattle with naturally occurring or synthetic sex hormones may enhance lean muscle growth and improve feed efficiency and is therefore a very cost effective procedure for cattle producers who have used it for decades in some Western countries, including the USA and Canada. The Joint Food and Agricultural Organisation/World Health Organisation (FAO/WHO) expert committee on food additives (JECFA) and the US Food and Drug Administration (FDA) considered, in 1988, that the residues found in meat from treated animals were safe for the consumers.We have re-evaluated the JECFA conclusions regarding the safety of estradiol residues in meat in the light of recent scientific data, with special emphasis on estradiol levels in prepubertal children. These levels are needed for estimates of the normal daily production rates of estradiol in children, who may be particularly sensitive to low levels of estradiol.In our opinion, the conclusions by JECFA concerning the safety of hormone residues in meat seem to be based on uncertain assumptions and inadequate scientific data. Our concerns can be summarized as follows. 1) The data on residue levels in meat were based on studies performed in the 1970 s and 1980 s using radioimmunoassay (RIA) methods available at the time. The sensitivity of the methods was generally inadequate to measure precisely the low levels found in animal tissues, and considerable variation between different RIA methods for measuring steroids exists. Therefore the reported residue levels may be subject to considerable uncertainty. 2) Only limited information on the levels of the various metabolites of the steroids was given despite the fact that metabolites also may have biological activity. 3) Reliable data on daily production rates of steroid hormones were and are still lacking in healthy prepubertal children. This lack is crucial as previous guidelines regarding acceptable levels of steroid residues in edible animal tissues have been based on very questionable estimates of production rates in children. Thus, even today the US FDA bases its guidelines on the presumably highly overestimated production rates in prepubertal children given in the JECFA 1988 report. 4) The possible biological significance of very low levels of estradiol is neglected.In conclusion, based on our current knowledge possible adverse effects on human health by consumption of meat from hormone-treated animals cannot be excluded.

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Section: Biological Effects Of Low Doses Of Sex Steroidsmentioning

confidence: 99%

Exposure to exogenous estrogens in food: possible impact on human development and health

1999

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“…Therapy to improve the growth velocity of these girls has included estrogens [1,2], anabolic steroids [3] and, more recently, growth hormone (GH) [4][5][6][7], the last of which seems also to increase their final height [4], Bone mineralization has been reported to be dimin ished in girls with Turner's syndrome [8,9], With the use of nonin vasive methods such as single-or dual-energy Xray absorptiometry [10,11] some studies have reported a reduction in mean radial bone mineral content and in lumbar spine bone mineral density (BMD) [9,12], while others have found normal lumbar BMD in patients with Turner's snydrome [13]. However, most of these studies involved adolescent age patients in which the lack of nor mal pubertal estrogen could contribute to the decreased bone mass.…”

mentioning

confidence: 99%

Bone Mineral Density of Prepubertal Age Girls with Turner’s Syndrome While on Growth Hormone Therapy

et al. 1995

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Bone mineral densities and growth velocities of young girls with Turner’s syndrome treated with recombinant human growth hormone at an age before the decreased levels of estrogens secondary to their ovarian failure could contribute to osteopenia were studied. Twelve patients with a mean chronological age of 8.9 ± 0.9 years and a mean bone age of 6.9 ± 0.8 years received growth hormone therapy for over 2 years (0.5 IU/kg/week s.c). Mean growth velocities increased significantly from a baseline level of 3.5 ± 0.4 cm/year to 6.4 ± 0.3 and 5.7 ± 0.4 cm/year at 12 and 24 months of therapy, while height SDS improved from -3.1 ± 0.4 at baseline to -2.7 ± 0.3 and -2.4 ± 0.3 at 12 and 24 months, respectively. Total bone calcium as well as cortical bone mineral density of our patients while on recombinant human growth hormone were similar to that of a control group of prepubertal healthy children paired for bone age and height; bone density of trabecular bone was however increased in our patients when compared to healthy controls (0.791 ± 0.04 vs. 0.669 ± 0.02 g/cm²; p < 0.025). We conclude from our study that the bone mineral status of young girls with Turner’s syndrome on growth hormone therapy seems to be normal.

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“…The effect of oestradiol on height velocity is dose-dependent reaching a maximum between 6 and 8 lg of ethinyl oestradiol. 10,11 Thereafter, and certainly by the time the 10 lg dose has been reached, height velocity declines because of a maturational effect of oestrogen on the epiphyseal growth plate. The time increments in Table 1 can be extended around the time of peak height velocity.…”

Section: Process Of Pubertal Inductionmentioning

confidence: 99%

How do you initiate oestrogen therapy in a girl who has not undergone puberty?

Hindmarsh

2009

Clinical Endocrinology

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SummaryThe physiology of puberty needs to be taken into consideration in the induction of puberty. Puberty is a relatively slow process and replacement therapy should mimic this. Long-term maintenance requires careful monitoring and long-term assessment of risk-benefit. This has not been appreciably defined in the adolescent population. Options for fertility need careful consideration and may depend on the adequacy of pubertal induction in terms of uterine development. A number of regimens are available for pubertal induction but the lack of comparisons makes it difficult to advocate for a particular regimen. There remain a number of areas of uncertainty, and future studies need to consider these issues and whether there are cardiovascular risk factor advantages to certain preparations. The long-term risks of breast and gynaecological malignancy remain uncertain. Long-term cohort studies are required to address these issues.

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Effect of low doses of estradiol on 6-month growth rates and predicted height in patients with Turner syndrome

Cited by 88 publications

References 15 publications

Exposure to exogenous estrogens in food: possible impact on human development and health

Exposure to exogenous estrogens in food: possible impact on human development and health

Bone Mineral Density of Prepubertal Age Girls with Turner’s Syndrome While on Growth Hormone Therapy

How do you initiate oestrogen therapy in a girl who has not undergone puberty?

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Effect of low doses of estradiol on 6-month growth rates and predicted height in patients with Turner syndrome

Cited by 88 publications

References 15 publications

Exposure to exogenous estrogens in food: possible impact on human development and health

Exposure to exogenous estrogens in food: possible impact on human development and health

Bone Mineral Density of Prepubertal Age Girls with Turner&rsquo;s Syndrome While on Growth Hormone Therapy

How do you initiate oestrogen therapy in a girl who has not undergone puberty?

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Bone Mineral Density of Prepubertal Age Girls with Turner’s Syndrome While on Growth Hormone Therapy