Aromatase inhibitors: Assessment of biochemical efficacy measured by total body aromatase inhibition and tissue estrogen suppression

Lønning, Per Eystein; Geisler, J

doi:10.1016/j.jsbmb.2007.09.017

Cited by 19 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These hormonal effects were far more pronounced with letrozole, with mean testosterone rising into or above the upper limit of normal for late pubertal or adult males, whereas levels were generally within the normal range during anastrozole treatment. The greater potency of letrozole was observed previously in pharmacokinetic studies, has been confirmed in the breast cancer literature and in whole body aromatization studies (28,29), and is implied in the pediatric growth trials, but this is the first direct comparison of the two drugs in a pediatric trial. Treatment with letrozole also resulted in higher gonadotropin levels (LH and FSH) compared with anastrozole, implying that the greater decrease in estradiol results in increased gonadotropins, further increasing testosterone levels (8).…”

Section: Discussionsupporting

confidence: 67%

Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

Neely

Kumar

Payne

et al. 2014

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Context: Aromatase inhibitors are used off-label to treat short stature in peripubertal boys.Objective: To investigate short-and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). Design:Patients are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years. They will be followed until they reach their final height. This is a preliminary report after 1 year of treatment.Setting: A single academic children's hospital outpatient clinic. Patients:Boys with age Ͼ10 years, bone age Յ14 years, clinical and hormonal evidence of central puberty, and either height Ͻ fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH).Intervention: Letrozole (2.5 mg) or anastrozole (1 mg) was administered orally each day. Main Outcome Measures:Hormonal and clinical parameters, growth velocity, and change in bone age and PAH.Results: Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 Ϯ 2.5 vs A 3.2 Ϯ 1.7 IU/L) and testosterone (1038 Ϯ 348 vs 536 Ϯ 216 ng/dL) with lower estradiol (2.8 Ϯ 2.8 vs 5.6 Ϯ 2.9 pg/mL) and IGF-1 (237 Ϯ 51 vs 331 Ϯ 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 Ϯ 3.5 vs 1.4 Ϯ 4.4 cm, p ϭ 0.03) after 1 year. Conclusions:We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group. A romatase is a cytochrome p450 enzyme that catalyzes the formation of C18 estrogens (estrone and estradiol) from C19 androgens (androstenedione and testosterone) (1). Two general types of pharmacologic aromatase inhibition have been developed to selectively inhibit estrogen synthesis: steroidal inhibitors compete with androstenedione for the substrate binding site, whereas nonsteroidal inhibitors bind to the heme group at the active site of the aromatase enzyme and block estrogen formation. Anastrozole and letrozole are the third generation

show abstract

Section: Discussionsupporting

confidence: 67%

Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

Neely

Kumar

Payne

et al. 2014

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

show abstract

“…In essence, the complex synergies between oestradiol, leptin, insulin and cortisol are directed towards the cyclic upregulation of p450 aromatase in adipose cells, uterine cells, prostate cells and breast cells, which significantly increases the production of intracellular oestradiol [a measurement that is far more accurate than serum oestradiol concentrations (Lonning and Geisler, 2008), as intracellular oestradiol levels can be 10-50 times higher than serum concentrations (Van Landeghem et al, 1985)] to increase ER-a stimulation (Cohen, 2008), to stimulate cell growth in breast and prostate tissue, to increase leptin levels (Yi et al, 2008) and to increase subcutaneous fat deposition and insulin resistance (Shin et al, 2007).…”

Section: The Process In Detailmentioning

confidence: 99%

“…The intracellular levels of aromatase (Lonning and Geisler, 2008) and oestradiol (Van Landeghem et al, 1985) reflect the highly oestrogenic microenvironment of breast cancers better than plasma levels, with intracellular levels being 10-50 times higher than plasma levels.…”

Section: Breast Cancermentioning

confidence: 99%

The role of oestrogen in the pathogenesis of obesity, type 2 diabetes, breast cancer and prostate disease

Williams

2010

European Journal of Cancer Prevention

View full text Add to dashboard Cite

A detailed review of the literature was performed in a bid to identify the presence of a common link between specific hormone interactions and the increasing prevalence of global disease. The synergistic action of unopposed oestrogen and leptin, compounded by increasing insulin, cortisol and xeno-oestrogen exposure directly initiate, promote and exacerbate obesity, type 2 diabetes, uterine overgrowth, prostatic enlargement, prostate cancer and breast cancer. Furthermore these hormones significantly contribute to the incidence and intensity of anxiety and depression, Alzheimer's disease, heart disease and stroke. This review, in collaboration with hundreds of evidence-based clinical researchers, correlates the significant interactions these hormones exert upon the upregulation of p450 aromatase, oestrogen, leptin and insulin receptor function; the normal status quo of their binding globulins; and how adduct formation alters DNA sequencing to ultimately produce an array of metabolic conditions ranging from menopausal symptoms and obesity to Alzheimer's disease and breast and prostate cancer. It reveals the way that poor diet, increased stress, unopposed endogenous oestrogens, exogenous oestrogens, pesticides, xeno-oestrogens and leptin are associated with increased aromatase activity, and how its products, increased endogenous oestrogen and lowered testosterone, are associated with obesity, type 2 diabetes, Alzheimer's disease and oestrogenic disease. This controversial break-through represents a paradigm shift in medical thinking, which can prevent the raging pandemic of diabetes, obesity and cancer currently sweeping the world, and as such, it will reshape health initiatives, reduce suffering, prevent waste of government expenditure and effectively transform preventative medicine and global health care for decades.

show abstract

“…Letrozole reversibly binds to cytochrome P450 of hemocrystallin that inhibits the syn-thesis of estrogen. In mammals, letrozole inhibits more than 98% of estrogen synthesis even to a nondetectable level (Lønning and Geisler, 2008). In the current study, letrozole decreased the level of estradiol to 1/3~1/2 of control levels in prelay pullets.…”

Section: Discussionmentioning

confidence: 99%

Letrozole inhibits the osteogenesis of medullary bone in prelay pullets

et al. 2010

View full text Add to dashboard Cite

This study was performed to investigate the effect of letrozole, an aromatase inhibitor, on osteogenesis of medullary bone in prelay pullets. Three hundred fifteen 95-d-old ISA prelay pullets were used. After 10 d of adaptation in the cages, 15 pullets were selected randomly to collect the serum and bone samples and the rest were randomly assigned to 2 groups with 3 replicates each. One group was control and the other was letrozole-treated, fed 0.5 mg of letrozole per prelay pullet per day for 18 d. The serum and bone samples from these birds were collected during the experiment. Estradiol and testosterone in serum were assayed using commercial RIA kits. The serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), Ca, and inorganic P were measured by an automatic biochemistry analyzer with commercial kits. The periosteum perimeter, endosteum perimeter, cortical bone index, cortical width, cortical bone area, and cortical area ratios of tibia were measured by transmitted scanner and a computer-assisted image analyzer. Our results showed that relative to the control-fed pullet, letrozole-fed pullets had reduced serum estrogen (57.5%), Ca (33.2%), ALP (33.6%), and TRAP (24.2%) and that values of serum estrogen, Ca, estrogen receptor expression, tibia radiographic density, serum ALP, and TRAP were all reduced (P < 0.05) and the serum P had a degressive trend in letrozole-treated groups. By contrast, the serum androgen and the tibia cortical bone index values were higher in the letrozole-treated group (P < 0.05). No differences were observed in the periosteum perimeter, endosteum perimeter, cortical width, and cortical area ratios of tibia between the 2 groups. The results showed that letrozole can inhibit the development of bone and medullary osteogenesis by inhibiting the synthesis of estrogen and its receptor in prelay pullets.

show abstract

Aromatase inhibitors: Assessment of biochemical efficacy measured by total body aromatase inhibition and tissue estrogen suppression

Cited by 19 publications

References 57 publications

Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

The role of oestrogen in the pathogenesis of obesity, type 2 diabetes, breast cancer and prostate disease

Letrozole inhibits the osteogenesis of medullary bone in prelay pullets

Contact Info

Product

Resources

About