Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

A case report of advanced male breast cancer with an objective response to tamoxifen treatment.

A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago. The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall. Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.

Aged↗

Muscle changes in brachial plexus birth injury with elbow flexion contracture: an MRI study.

BACKGROUND: Muscle pathology of the arm and forearm in brachial plexus birth injury (BPBI) with elbow flexion contracture has not been evaluated with MRI. OBJECTIVE: To determine whether limited range of motion of the elbow in BPBI is correlated with specific patterns of muscular pathology. MATERIALS AND METHODS: For 15 BPBI patients, total active motion (TAM) of the elbow (extension-flexion) and the forearm (pronation-supination) were measured. MRI of the elbow joints and musculature allowed assessment of elbow congruency. Fatty infiltration and size reduction of the muscles were graded semiquantitatively. RESULTS: Mean TAM of the elbow was 113 degrees (50 degrees-140 degrees) and that of the forearm 91 degrees (10 degrees-165 degrees). The greater the size reduction of the brachioradialis muscle, the more diminished was elbow TAM. The more extensive the BPBI and muscle pathology of the pronator teres muscle, the more limited was the TAM of the forearm. Pathology of the supinator and brachialis muscles was evident in every patient. CONCLUSION: Extensive BPBI may result in marked limitation of TAM. Elbow flexion contracture seems to be caused mainly by brachialis muscle pathology. Prosupination of the forearm is better preserved when the pronator teres is not severely affected. MRI can reliably show the extent of muscle pathology in BPBI.

Adolescent↗

Induction of apoptosis in human prostate stromal cells by 4-hydroxytamoxifen: an alternative therapy for benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a disease of the aging male. In BPH, the imbalance of cell proliferation and programmed cell death (apoptosis) leads to continuous stromal growth. Common medication interrupts stromal cell proliferation but has only little effect on inducing stromal cell apoptosis. In this study, we investigated tamoxifen (TAM) and 4-hydroxytamoxifen (OHT) for their ability to induce apoptosis in human prostate stromal cells (PrSC) in vitro. After the incubation of PrSC with different concentrations of TAM or OHT, the cytotoxic effect was measured using an MTT-assay. The induction of apoptosis after OHT treatment was investigated by FACS-analysis (annexin V FITC staining) and Western blot (PARP-1 cleavage, BCL-2 and BAX-alpha expression). The administration of TAM at concentrations of 0-20 microM had very little effect on cell viability as measured by MTT assay. In contrast, the use of 10-20 microM OHT led to a significant decrease in cell viability. The binding of annexin V FITC to apoptotic cells was demonstrated by FACS-analysis. The induction of apoptosis was further proven by Western blot of PARP-1 protein cleavage and the expression of the anti-apoptotic BCL-2 and the pro-apoptotic BAX-alpha proteins. In conclusion, our data clearly demonstrate, that the administration of OHT at concentrations from 10-20 microM induced apoptosis in human PrSC. The more effective induction of apoptosis with OHT compared with TAM could very well explain the results of clinical studies showing no clinical effect of TAM treatment on BPH. Furthermore, our results, if reproducible in vivo, could open new avenues for the treatment of BPH by local administration of OHT in apoptosis-inducing concentrations.

Apoptosis↗

Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma.

Angiogenic and anti-angiogenic factors, secreted by tumor, inflammatory, and stromal cells play an important role in regulation of neovascularization. Among the most important of these is vascular endothelial growth factor (VEGF), a specific mitogen for endothelium, which increases vascular permeability and induces proteolytic enzymes necessary for vascular remodeling. Tumor-associated macrophages (TAMs) can express complex functions related to tumor biology, including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define, using immunohistochemical analysis, the microvessel density (MVD), VEGF expression, and TAMs level in 97 human invasive ductal breast carcinomas not otherwise specified (NOS), investigate a possible relationship between them and then correlate their values with tumor grade, mitotic activity index (MAI), tumor size and lymph-node status. Statistical analysis showed a strong positive relationship between MVD and VEGF expression ( P<0.001). Furthermore, both MVD and VEGF expression were significantly correlated with tumor grade and lymph-node status, and TAMs infiltration with MAI. TAM level showed a significant positive connection with VEGF expression and MVD. These in situ observations suggest that VEGF stimulates angiogenesis in human invasive ductal breast carcinoma NOS and attracts macrophages to the tumor locus, which then may be involved in angiogenesis promotion. The expression of this angiogenic molecule, and MVD and TAM level, can provide additional prognostic significance and help in the identification of patients who need postoperative adjuvant therapy.

Breast Neoplasms↗

Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma.

PURPOSE AND METHOD: Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage infiltration of tumor tissue. Tumor-associated macrophages (TAMs) are a population of mononuclear phagocytic cells that can have a complex function in tumor biology. The aim of this study was to determine the possible correlation between parenchymal MCP-1 expression and TAM level by immunohistochemical analysis of 97 invasive ductal breast carcinomas, not otherwise specified (NOS), and to investigate their relation with tumor size, histological grade, mitotic activity index (MAI) and lymph node status. Secondly, the MCP-1 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in eight samples of normal breast tissue and 27 samples of invasive breast carcinomas and compared with TAMs. RESULTS: MCP-1 immunoreactivity was present in tumor cells (17/97), but also in TAMs, fibroblasts and endothelial cells. The statistical analysis did not show a significant correlation between MCP-1 expression in tumoral epithelium and tumor size, histological grade, MAI, lymph node status or TAMs. The results of RT-PCR showed that, in all cases of breast carcinomas (27/27) and the majority of normal breast tissues (7/8), the number of detected MCP-1 cDNA copies was above the detection limit. However, carcinomas showed higher levels of MCP-1 mRNA than normal breast tissue. Nevertheless, the statistical analysis did not find a significant correlation between MCP-1 expression and macrophage infiltrations. CONCLUSION: These results indicate that MCP-1 is probably not the only and/or crucial factor involved in macrophage attraction to tumor locus in breast carcinoma.

Breast↗

Predictions of onset of crystallization from experimental relaxation times I-correlation of molecular mobility from temperatures above the glass transition to temperatures below the glass transition.

PURPOSE: Predicting onsets of crystallization at temperatures below T (g), from data above T (g), would require that the correlation between crystallization onset and mobility is same above and below T (g), and the techniques being used to measure mobility above and below T (g) are measuring essentially the same kind of mobility. The aim of this work is to determine if the relaxation times obtained using different techniques (DSC, TAM) below T (g) correlate with relaxation time obtained above T (g) using dielectric spectroscopy. METHODS: Model compounds for this work were chosen based on their varied DeltaH (f), DeltaC (p)(T (g)) and H-bonding in crystalline state vs. amorphous state. Relaxation times above T (g) were determined by the simultaneous fit of real and imaginary permittivity to the Cole-Davidson model. Tau and beta below T (g) were determined using isothermal microcalorimetry (TAM) or MDSC. MDSC was used to calculate Kauzmann temperature and strength of the glass using established relationships. RESULTS: Indomethacin, nifedipine and flopropione showed Arrhenius temperature dependence throughout the entire temperature range and extrapolation of tau ( beta ) measured above T (g) by dielectric relaxation agreed with tau ( beta ) measured below T (g) by TAM/MDSC. Ketoconazole, however, showed the expected VTF behavior. For at least two compounds compared (indomethacin and ketoconazole), relaxation times measured by TAM and MDSC did not agree, with TAM giving significantly lower values of tau ( beta ), but TAM and MDSC relaxation times appeared to extrapolate to a common value at T (g). CONCLUSIONS: It was found that, for all cases studied, relaxation time constants determined above and below T (g) did appear to extrapolate to the same value around T (g) indicating that molecular mobility measured above and below T (g) using different techniques is highly correlated.

Calorimetry↗

Identification of the cytochrome P450 IIIA family as the enzymes involved in the N-demethylation of tamoxifen in human liver microsomes.

The antiestrogen tamoxifen (Tam or Nolvadex, ICI)-Z-1-[4-[2-(dimethylamino) ethoxy]phenyl]-1,2-diphenyl-1-butene is widely used in treatment of hormone-dependent breast cancer. The drug is extensively metabolized by cytochrome P450 dependent hepatic mixed function oxidase in man, yielding mainly the N-desmethyl metabolite (DMT). This study has been carried out to determine the P450 enzyme involved in the N-oxidative demethylation of Tam in microsomal samples from 25 human livers (23 adults, two children). This metabolic step was inhibited by carbon monoxide up to 75%. Tam was demethylated into DMT with an apparent Km of 98 +/- 10 microM; rates varied between 37 and 446 pmol/min/mg microsomal protein. These metabolic rates were strongly correlated with 6 beta-hydroxylation of testosterone (r = 0.83) and erythromycin N-demethylase (r = 0.75), both activities known to be associated with P450 IIIA enzyme. To further assess whether or not the Tam demethylation pathway is catalysed by the same P450, the inhibitory effect of TST on this reaction was determined. The competitive inhibition had an apparent Ki of 100 +/- 10 microM. Drugs such as erythromycin, cyclosporin, nifedipine and diltiazem were shown to inhibit in vitro the metabolism of tamoxifen. Furthermore the P450 IIIA content of liver microsomal samples, measured by Western blot technique using a monoclonal P450NF (nifedipine) antibody, was strongly correlated with DMT formation (r = 0.87). Tam N-demethylase activity was inhibited by more than 65% with polyclonal anti-human anti-P450NF. All these in vitro observations establish that a P450 enzyme of the IIIA sub-family is involved in the oxidative demethylation of tamoxifen in human liver.

Animals↗

Evaluation of estrogen receptor, antiestrogen binding sites and calmodulin for antiestrogen resistance of two clones derived from the MCF-7 breast cancer cell line.

Estrogen receptor (ER), antiestrogen binding sites (AEBS) and calmodulin (CaM) are potential targets of antiestrogen (AE) action. To analyse further which of these targets are primarily involved in the antiproliferative activity of these drugs against human breast cancers, two cell clones, namely the RTx6 and LY-2 variants, selected from MCF-7 cells for their resistance to high doses of tamoxifen (TAM) and the Keoxifen (KEO) analog LY 117018, respectively, were studied for their sensitivity to hydroxytamoxifen (OH-TAM) and KEO as well as the strong calmodulin antagonist calmidazolium. The effects of these drugs on both cell growth and progesterone receptor (PgR) concentration were assessed. Binding properties for ER, AEBS and CaM of each compound were also measured. Our results confirmed that basal growth of RTx6 and LY-2 cells was more resistant to OH-TAM and KEO than parent MCF-7 cells, although both displayed a significant inhibition at the highest doses assessed. In regard to calmidazolium inhibition, each variant behaved as did the MCF-7 line indicating that a modification at the CaM level was not responsible for their lower sensitivity to AEs. Nor could the association of CaM to ER which did not differ among all cell lines. Resistance of these variants was not related to AEBS in view of the total lack of such sites in RTx6 cells. However, under estrogenic growth stimulation such sites may play some role, since LY-2 cells in the presence of estradiol displayed a real antiestrogen-resistant pattern while RTx6 cells were more sensitive than MCF-7 cells to OH-TAM. This property was not found in the antagonism against estradiol-induced PgR synthesis which was observed with each variant. Thus the PgR concentration of RTx6 cells was strongly down-regulated by OH-TAM and KEO and reduced in LY-2 cells to the same extent as in MCF-7 cells. All these observations show that AE resistance is not entirely related to ER mediated events and that alterations at the ER and CaM levels are unlikely to account for the lower AE sensitivity of the variants investigated.

Binding Sites↗

An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain.

Ovariectomized CFW mice were treated with tamoxifen (TAM) alone or in combination with estradiol benzoate (EB) to determine its ability to promote/block lordotic behavior and the induction of hypothalamic progestin receptors (PR). Across a range of doses, TAM plus progesterone treatment did not activate female sexual behavior. When given with EB, TAM suppressed lordotic behavior in a dose-dependent fashion. TAM did not induce PR when given alone and it completely blocked the ability of EB to induce PR. It therefore appears that for these responses TAM functioned as a pure antagonist in the female mouse brain, although the degree of its antiestrogenicity varied with the response under consideration. A potential mechanism mediating this differential effectiveness is discussed.

Animals↗

The inhibition of prolactin synthesis in GH3 rat pituitary tumor cells by monohydroxytamoxifen is associated with changes in the properties of the estrogen receptor.

E2 (1 nM) stimulated the synthesis of PRL in GH3 cells. OH TAM (100 nM) did not affect basal PRL synthesis, but completely inhibited the increase produced by 1 nM E2. [3H]E2 and [3H]OH TAM both bound to the cytosolic 8S ER and these were split into 4S subunits on sucrose gradients containing 0.4 M KCl. By comparison, ER complexes extracted from nuclei of GH3 cells cultured in media containing [3H]E2 or [3H]OH TAM both sedimented at 5S on sucrose gradients containing 0.4 M KCl. Both 4S and 5S ER complexes were recognized by the monoclonal antibody D547 which increased their sedimentation coefficients to 8-9S. In contrast, a polyclonal antibody raised to calf uterine ER in the goat, interacted with the cytosolic ER so that the binding of [3H]E2 was inhibited but the binding of [3]OH TAM was only slightly reduced. A molecular model is proposed to describe the binding of E2 and OH TAM to the ER that might contribute to an understanding of estrogen and antiestrogen action.

Animals↗

Binding of estrogen and antiestrogen in uterine cell nuclei: in vivo autoradiographic studies.

The in vivo binding of antiestrogen in nuclei within the uterine stromal, epithelial and myometrial tissue compartments was compared to that of estrogen 2-48 h after injection. Tissue binding and retention of radioactivity was also studied. Immature rats were injected s.c. with 0.36 microgram [3H]hydroxytamoxifen [( 3H]TAM(OH] or 0.24 microgram [3H]estradiol [( 3H]E2) in oil. At 2, 4, 8, 12, 24 and 48 h after injection, uteri were processed for thaw-mount autoradiography and, along with other tissues, for liquid scintillation counting. After [3H]TAM(OH) injection total radioactivity in uterus, cervix, vagina and liver reached peak levels by 8 h then decreased slowly so that by 48 h radioactivity still remained in the tissues. At all time intervals, the levels of radioactivity in heart and muscle remained low. After [3H]E2 injection radioactivity in uterus, cervix and vagina reached peak levels between 2 and 4 h then decreased rapidly so that by 12 h radioactivity was low and essentially the same as in liver, heart and muscle. These results were paralleled by the time course of nuclear binding of [3H]TAM(OH) and [3H]E2 in the uterine cell types: peak levels occurred at 8 h and 4 h, respectively. Nuclear binding was still present 48 h after [3H]TAM(OH) injection but was absent by 24 h after [3H]E2 injection. Different uterine cell types bound different amounts of both the drug and the hormone. After [3H]TAM(OH) injection the decreasing order of labeling intensity in the tissue compartments was stroma, myometrium, epithelium; in contrast, that after [3H]E2 injection was stroma, epithelium, myometrium. The results indicate that the dissimilar nuclear binding kinetics of estrogen and antiestrogen are influenced by the pharmacokinetics but the uterine cell types may also influence binding kinetics.

Animals↗

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors.

UNLABELLED: We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modifications induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17 beta-estradiol (E2) at both low (0.1 micrograms/kg) and high (20 micrograms/kg) doses confirmed its ability to increase the number of striatal 3H-Spiperone (3H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E2, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophyseal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. IN CONCLUSION: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of its antiestrogenic activity.

Animals↗

Tamoxifen and medroxyprogesterone therapy for advanced endometrial carcinoma.

We have studied the response rates and survival of a group of 93 patients with Stage III or IV endometrial adenocarcinoma after random allocation to therapy with tamoxifen (TAM) 20 mg twice daily (n = 45) or medroxyprogesterone acetate (MPA) 1 g/wk intramuscularly (n = 48). The patients were examined every 4 months. In the non-responders and in those who relapsed, combination therapy with TAM and MPA was given. Twenty-four of 45 (53.4%) responded to TAM alone, 27 of 48 (56.2%) responded to MPA alone. Of the responders 23 later relapsed in the TAM group and 24 in the MPA group and of these 14 (60.8%) and 15 (62.5%), respectively, responded to the combination therapy. Of the original 21 non-responders to MPA alone, 10 responded to the combination (47.6%) and 11 (52.4%) did not; the comparable figures for the TAM alone group were 13 (61.9%) and 8 (38.1%), respectively. Survival rates were much higher in the differentiated than in the undifferentiated carcinomas. In conclusion, we feel that the efficacy, and the few side-effects of these drugs used alone and particularly when used in sequential combination, make them a very attractive treatment for advanced endometrial adenocarcinoma.

Adenocarcinoma↗

Influence of chemopreventive agents on estradiol metabolism and mammary preneoplasia in the C3H mouse.

The C3H strain of mouse has a high incidence of murine mammary tumor virus-induced mammary tumors, and tumorigenesis progresses via the intermediate formation of the preneoplastic, hyperplastic alveolar nodules (HANs). The C3H mouse also exhibits an elevation in 16 alpha-hydroxylation of estradiol which remains unaltered in relation to the age or presence of tumor, but which is detectable well before the emergence of overt mammary cancer. This metabolic pathway leads to the formation of 16 alpha-hydroxyestrone (16 alpha-OHE1), a putative promoter of mammary cancer. The present study examines the effect of two prototype chemopreventive agents, tamoxifen (TAM) and N-(4-hydroxyphenyl)retinamide (HPR), on 16 alpha-hydroxylation of estradiol and on the growth of HANs. Treatment with TAM, HPR, or a combination of TAM and HPR for 4 weeks in 6- to 8-week-old C3H mice resulted in a consistent elevation in the 16 alpha-hydroxylation pathway of estradiol metabolism relative to the placebo control group (20.50% +/- 2.35%, 21.46% +/- 1.49%, 18.00% +/- 1.75%, and 12.64% +/- 1.45% SD, respectively) and in a significant decrease in the mean frequency of HANs per mammary gland (1.4, 2.1, 0.0, and 5.8, respectively). Mice without any experimental manipulation exhibited an age-dependent progressive increase in HAN frequency from 1.5 per gland at 4 weeks of age to 12.1 per gland at 24 weeks of age. Administration of TAM, HPR, or a combination of TAM and HPR up to 22 weeks of age resulted in a continued suppression of HAN frequency, and the two agents in combination exerted an additive effect on the suppression of HAN development.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The effect of tamoxifen on the reproductive traits in White Leghorn cockerels.

Fifty White Leghorn male chicks were divided into five equal groups of ten chicks each. Beginning at two weeks of age they were injected on each alternate day as follows: corn oil as a vehicle control or 0.5, 1.0, 5.0, or 10.0 mg tamoxifen/kg/b.wt. The whole experimental period lasted until twelve weeks of age. The two lowest doses of tamoxifen (TAM) enhanced comb growth, while the highest dose suppressed it. The two lowest doses of TAM also caused an earlier increase in sexual activity of the chicks, and precocious production of semen. At nine weeks of age the 0.5 and 1.0 mg doses of TAM increased plasma testosterone to a level three times higher than in the controls. This effect was not observed with the highest dose of TAM. At 12 weeks of age the chicks treated with 1 mg TAM had larger testes than the controls and produced three times more sperm per ejaculation. At this stage chicks treated with the highest dose of tamoxifen produced less sperm than the control and had smaller testes and adenohypophyses.

Aging↗

Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor.

A potential mechanism is described by which a growth factor may prevent the action of antiestrogens or reactive the growth of hormone-responsive breast carcinoma in patients undergoing tamoxifen (TAM) treatment. Epidermal growth factor (EGF)-stimulated growth (10(-8) M EGF) was assayed in the MCF-7 breast cancer cell line in the presence of various concentrations (10(-10) to 10(-6) M) of three antiestrogens, 4-hydroxytamoxifen (OH TAM), TAM and ICI 164384. In each case, the EGF-stimulated increases in DNA were not inhibited by the antiestrogen. OH TAM and ICI 164384 inhibited estradiol (E2) stimulated cell proliferation in a dose-related fashion. However, in the presence of both E2 and EGF, these two antiestrogens inhibited E2 effects only; EGF promotion of growth was unaffected. Pretreatment of MCF-7 cells for 2 days with either OH TAM or ICI 164384 did not inhibit EGF-induced increases in cell proliferation. We propose that eventual antiestrogen therapeutic failure may be caused by the paracrine influences of growth factors from neighboring cells.

Breast Neoplasms↗

Augmentation of cytotoxicity using combinations of interferons (types I and II), tumor necrosis factor-alpha, and tamoxifen in MCF-7 cells.

The cytotoxic effect of a combination of interferons (type I and II) and tumor necrosis factor (TNF), with an antiestrogenic drug, tamoxifen (TAM), was investigated in the estrogen receptor positive human breast carcinoma cell line, MCF-7. Cytotoxicity was measured by the MTT assay. In an attempt to define the molecular basis for the interaction between the interferons (IFNs) and TNF or any one of the cytokines with TAM, the induction characteristics of a number of IFN-induced mRNAs in response to IFNs, TNF, and TAM were studied. We observed an augmentation of the cytotoxic effect of TNF when it was combined with TAM. There appears to be an overlap in signalling mechanisms of IFNs and TNF as two of the IFN-inducible genes, 1-8 and 6-16 are also induced by TNF. mRNA 1-8 was induced by both IFN-alpha (type I) and IFN-gamma (type II). We conclude that TNF potentiates the cytotoxic effects of TAM in MCF-7 cells and that the three cytokines IFN-alpha, IFN-gamma, and TNF share some pathways that lead to specific induction of some cytokine responsive genes.

Antineoplastic Combined Chemotherapy Protocols↗

Suppression of serum insulin-like growth factor-1 levels in breast cancer patients during adjuvant tamoxifen therapy.

Serial IGF-1 levels in patients prior to and during adjuvant tamoxifen (TAM) treatment were followed in a retrospective study. Serum IGF-1 levels were determined by radioimmunoassay in 19 patients taking TAM and 19 controls, matched for age, body weight and other treatments. IGF-1 levels at 2 years were significantly lower in TAM patients (P < or = 0.05) compared to control patients. We observed a significant mean drop from pretreatment to treatment IGF-1 levels by 19.9% in the TAM group (P < or = 0.005), but also noted a mean 11.4% decline in the control group (P < or = 0.025). A subgroup analysis suggested that premenopausal were relatively resistant to the IGF-1 lowering effects of TAM as compared to postmenopausal women.

Adult↗