Fang-Ping Chen

Efficacy of imiquimod 5% cream for persistent human papillomavirus in genital intraepithelial neoplasm.

OBJECTIVE To assess the clinical response to imiquimod 5% cream in patients with persistent human papillomavirus (HPV) infection after treatment of genital intraepithelial neoplasia. MATERIALS AND METHODS Imiquimod 5% cream was applied to treat 76 women with persistent HPV after surgical therapy for cervical or vaginal intraepithelial neoplasia (CIN or VAIN). One sachet of cream was placed in the cervical os and vagina with an applicator twice weekly for 8 weeks. Repeated HPV evaluation and Papanicolaou (Pap) smear and/or biopsy were performed 3 months following treatment completion. RESULTS In total, 58 of the 76 patients (76.3%) were clear of HPV infection and had normal Pap smears after administration of imiquimod cream. Although atypia or mild dysplasia was noted in 15 of the 18 patients (83.3%) with persistent HPV infection after imiquimod cream treatment, the degree of severity was noticeably less than the initial diagnosis in most of these patients. Persistent HPV positivity was observed in 12 of the 64 patients (18.8%) with CIN and 6 of the 12 patients (50.0%) with VAIN. CONCLUSION Topical imiquimod 5% cream may be beneficial in most cases of genital intraepithelial neoplasia, especially CIN, with persistent HPV following surgical treatment.

Factors that influence changes in mammographic density with postmenopausal hormone therapy.

OBJECTIVE To evaluate the relationship between mammographic density and clinical factors in postmenopausal women using hormone therapy (HT). MATERIALS AND METHODS Retrospective study of 467 postmenopausal women who received continuous estrogen or estrogen-progestin HT and had regular mammography between 1994 and 2001. A detailed clinical history was recorded, including age at start of HT, age at menopause, years from onset of menopause to start of HT, body mass index (BMI), and duration and regimens of HT. RESULTS After adjustment for the effects of other variables, age at the start of HT and BMI were inversely associated with breast density (p = 0.0025 and < 0.001, respectively). In contrast, duration of HT was positively related to mammographic density (p<0.001). Although the mean density was significantly increased after 4 years of HT in women receiving combined HT compared with those using estrogen alone, after adjustment for the effects of other variables, the correlation between mammographic density and regimen of HT (combined HT vs. estrogen alone) did not reach the significance level of 0.05. CONCLUSION Higher mammographic density was associated with longer use of HT, especially in younger post-menopausal women and those with lower BMI.

Effects of estradiol and progestogens on human breast cells: Regulation of sex steroid receptors

OBJECTIVES To examine the effects of 17β-estradiol (E2) and progestogens, used in hormone therapy, on estrogen receptors (ER), progesterone receptors (PR), and human breast tumor cell growth. MATERIALS AND METHODS MCF-7 cells were incubated in pure E2 (1 nM and 10 nM) as well as in E2 in conjunction with 10 nM progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NET), and cyproterone acetate (CPA). Cell proliferation, apoptosis, expression of caspase-3, and both ER and PR isoforms were evaluated. RESULTS Caspase-3 was significantly diminished in cultures with only E2, whereas ERα significantly increased. A significant increase of caspase-3 in addition to the entire abolishment of E2-induced augmentation of ERα was observed in 1 nM E2 plus MPA and 10 nM E2 plus NET, whereas PR isoform B (PRB) was significantly increased. The ratios of apoptosis: proliferation significantly increased in 1 nM E2 plus progestogens (except P4) and 10 nM E2 plus NET. The changes of the PRA/PRB ratio were inversely related to the changes of the apoptosis to proliferation ratio. Significant increase of ERβ and PRB was noted in the E2 plus MPA or NET, in addition to a significant increase of ERα and decrease of PRA in the E2 plus CPA, as well as an increase of ERα and decrease of PRA and PRB in the E2 plus P4. CONCLUSIONS The combination of E2 and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.

HORMONE THERAPY AND CARDIOVASCULAR DISEASE

As in other Western countries, cardiovascular disease (CVD) is the leading cause of death among women in Taiwan, exceeding the mortality from cervical or breast cancer. Women generally present with CVD after menopause and later than men, since menopause-related estrogen deficiency has been considered to be associated with an increased risk for CVD. Thus, coronary artery diseases and stroke are the two main contributors of mortality among postmenopausal women. Observational studies have reported a reduction in coronary artery disease risk after hormone therapy (HT) ranging from 31-44%. However, recent randomized controlled trials that evaluated the effect of HT on primary and secondary CVD prevention have questioned the efficacy of HT, despite confirming the lipid-lowering effect of estrogen. However, a cluster of factors are responsible for the genesis and progression of CVD. Until we further evaluate their specific actions and how these different factors interact, the issue related to HT and cardiovascular risk will remain unsettled. Since these studies have contributed to our understanding of the benefits and risks associated with HT, HT use should be individualized after consideration of the condition of each postmenopausal patient. Ideally, the efficacy of different preparations and dosages of HT in postmenopausal women who are at risk of CVD, before atheromatous lesions have developed, should be investigated.

Application of the World Health Organization Fracture Risk Assessment Tool to predict need for dual-energy X-ray absorptiometry scanning in postmenopausal women.

OBJECTIVE To evaluate the efficacy of the World Health Organization Fracture Risk Assessment Tool, excluding bone mineral density (pre-BMD FRAX), in identifying Taiwanese postmenopausal women needing dual-energy X-ray absorptiometry (DXA) examination for further treatment. MATERIALS AND METHODS The pre-BMD FRAX score was calculated for 231 postmenopausal women who participated in public health education workshops in the local Keelung community, Taiwan. DXA scanning and vertebral fracture assessment (VFA) were arranged for women classified as intermediate or high risk for fracture using the pre-BMD FRAX fracture probability. RESULTS Pre-BMD FRAX classified 26 women as intermediate risk and 37 as having high risk for fracture. Subsequent DXA scans for these 63 women showed that 36 were osteoporotic, 19 were osteopenic, and eight had normal bone density. Concurrent VFA revealed 25 spine factures in which 14 were osteoporotic, seven were osteopenic, and four had normal bone density. The efficacy of the pre-BMD FRAX score to identify those patients with low bone mass by DXA was 87.3% (55/63). When VFA was combined with BMD to identify those patients with high risk (osteopenia, osteoporosis, or spinal fracture), the efficacy of the pre-BMD score increased to 93.7% (59/63). According to the National Osteoporosis Foundation, the overall concordance between pre-BMD FRAX and BMD, expressed through the kappa index, was 0.967. Compared with the evaluation when BMD was used alone, there was a significant increase in efficacy in identifying women who need treatment using BMD plus VFA or FRAX plus BMD. Furthermore, the highest efficacy was achieved when FRAX with BMD and VFA was used. CONCLUSION The pre-BMD FRAX score not only efficiently predicts postmenopausal patients who are potentially at risk and might require treatment but also reduces unnecessary DXA use. Concurrent VFA during DXA use increases spine fracture detection. This improvement in diagnostic efficacy allows clinicians to provide the most appropriate therapeutic recommendation.

Effects of phthalates on normal human breast cells co-cultured with different fibroblasts

Whether or not phthalates play a role in breast carcinogenesis remains to be determined. The goal of this study was to explore the effects of phthalates on the growth of normal MCF-10A breast cells modulated by breast fibroblasts. Fibroblasts were derived from normal mammary tissue adjacent to both estrogen receptor (ER) positive and negative primary breast cancers, which were grown separately from nontumorigenic MCF-10A epithelial cells. MCF-10A co-culture cells were treated with 10 nM 17β-estradiol (E2), Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP) (10 and 100 nM). After incubation for 120 hours, the cells were harvested and extracted for MTT assay. Western blot analysis was used to evaluate the proliferative pathway proteins and the effects on ER α. Only fibroblasts from ER (+) breast cancer significantly stimulated proliferation of MCF-10A cells. Exposure of the co-culture to E2, BBP, DBP, DEHP, and E2 combined with one of these phthalates resulted in significantly increased cell proliferation, as well as proliferating cell nuclear antigen (PCNA) and ER α expressions. The present study demonstrates that phthalates express a significant influence in fibroblast–epithelial interactions, similarly to the effects of E2 on breast cells. The effects of phthalates on normal breast cells depend upon ER modulating actions. In breast carcinogenesis, phthalates should be considered as having endocrine disrupting potential, even at low concentrations.

Correlation of quality of life with risk factors for first‐incident hip fracture in postmenopausal women

The aim of this study was to identify the correlation between health‐related quality of life (HRQOL) and risk factors of first‐incidence hip fracture in postmenopausal women.

Effect of Chemotherapy on Dual-Energy X-ray Absorptiometry (DXA) Body Composition Precision Error in Head and Neck Cancer Patients

BACKGROUND Precision error in dual-energy X-ray absorptiometry (DXA) is defined as difference in results due to instrumental and technical factors given no biologic change. The aim of this study is to compare precision error in DXA body composition scans in head and neck cancer patients before and 2 months after chemotherapy. METHODOLOGY A total of 34 male head and neck cancer patients with normal body mass index (BMI) were prospectively enrolled and all patients received 2 consecutive DXA scans both before and after 2 months of chemotherapy for a total of 4 scans. The precision error of 3 DXA body composition values (lean mass, fat mass, and bone mineral content) was calculated for total body and 5 body regions (arms, legs, trunk, android, and gynoid). Precision errors before and after treatment were compared using generalized estimating equation model. RESULTS There was no significant change in precision error for the DXA total body composition values following chemotherapy; lean mass (0.33%-0.40%, p = 0.179), total fat mass (1.39%-1.70%, p = 0.259) and total bone mineral content (0.42%-0.56%, p = 0.243). However, there were significant changes in regional precision error; trunk lean mass (1.19%-1.77%, p = 0.014) and android fat mass (2.17%-3.72%, p = 0.046). CONCLUSIONS For head and neck cancer patients, precision error of DXA total body composition values did not change significantly following chemotherapy; however, there were significant changes in fat mass in the android and lean mass in the trunk. Caution should be exercised when interpreting longitudinal DXA body composition data in those body parts.