Peter F. Schnatz

Clinical significance of atypical glandular cells on cervical cytology.

OBJECTIVE: To evaluate the prevalence and histologic outcomes of patients with atypical glandular cells of undetermined significance (AGUS), diagnosed by Pap test, and concurrent risk factors. DATA SOURCES: A PubMed/MEDLINE/Ovid HealthStar search of the English literature was conducted from January 1988 through March 2004. METHODS OF STUDY SELECTION: The search criteria included the terms “atypical glandular cells of undetermined significance,” “AGUS,” or “AGC.” All studies investigating the clinical significance of patients with an AGUS Pap test were included, except for those where consecutive Pap tests were not studied. Diagnostic outcomes were then determined. TABULATION, INTEGRATION, AND RESULTS: Of the 916 studies identified, 24 met our inclusion criteria. Of the 2,389,206 Pap tests included in these studies, 6,829 (0.29%) had AGUS. Follow-up was available for 3,890 tests. These data showed the following rates of pathology: 8.5% low-grade squamous intraepithelial lesions (LSIL), 11.1% high-grade squamous intraepithelial lesions (HSIL), 2.9% adenocarcinoma in situ, 1.4% endometrial hyperplasia, and 5.2% malignancy. The most common malignancies were endometrial adenocarcinoma (57.6%), cervical adenocarcinoma (23.6%), ovarian and fallopian tube carcinoma (6.4%), squamous cell carcinoma of the cervix (5.4%), and other (6.9%). Of the AGUS Pap tests, the remaining 71.0% corresponded to benign findings, including reactive changes, polyps, and normal histology. Patients with AGUS, which favors a neoplastic process, or with a concurrent ASCUS have a greater likelihood of disease. CONCLUSION: Histologic diagnosis showed that 29.0% of these Pap tests had findings requiring follow-up or therapeutic intervention, including a 5.2% rate of malignancy. Based on these findings, 99.6% of the diagnoses are within the region of surveillance when AGUS Pap tests are evaluated with colposcopy and directed biopsy, endocervical curettage, an endometrial biopsy in patients with risk factors for endometrial cancer, and pelvic examination.

The North American Menopause Society recommendations for clinical care of midlife women

In celebration of the 25th anniversary of The North American Menopause Society (NAMS), the Society has compiled a set of key points and clinical recommendations for the care of midlife women. NAMS has always been a premier source of information about menopause for both healthcare providers and midli

Dysplasia associated with atypical glandular cells on cervical cytology

OBJECTIVES: To estimate the rates of and identify risk factors for disease in women with atypical glandular cells of undetermined significance (AGUS). METHODS: From 1998–2001, 477 Pap tests at Hartford Hospital were classified as AGUS and met the inclusion criteria of this study. Findings were evaluated for 2 years from the initial test. Disease was defined as histology results with a finding of high-grade squamous intraepithelial lesion or greater. RESULTS: Disease was diagnosed in 9% of the women, including malignancy in 3%. Women with malignant-appearing AGUS Pap tests had a higher rate of disease (29%) than women with benign-appearing (5%, P < .01) and unspecified AGUS Pap tests (13%, P < .03). Malignancies were associated with all subclassifications of AGUS Pap tests. Women aged less than 35 years were more likely to have disease than women aged 35 years or older (P < .02). Most women aged younger than 35 years had a squamous abnormality, whereas women aged 35 years or older had a greater diversity of squamous and glandular lesions and accounted for all cases of endometrial cancer, adenocarcinoma in situ, and cervical adenocarcinoma. Women with persistent AGUS Pap tests had a 31% rate of disease. The rate of disease among women with AGUS Pap tests collected by liquid-based cytology was 11%, compared with 6% among samples collected by the conventional method. CONCLUSION: These data suggest that women with atypical glandular cells are at substantial risk for dysplasia and malignancy. The rate of disease varies with the method of Pap test collection, age, presence of persistent AGUS Pap tests, and AGUS subclassification. LEVEL OF EVIDENCE: II-3

Parathyroidectomy in the third trimester of pregnancy.

The objective of this study was to estimate the incidence of complications when primary hyperparathyroidism (PHPT) is treated by parathyroidectomy in the third trimester of pregnancy. After searching the literature published through/including January 2005, we identified and analyzed 16 cases of PHPT treated surgically after 27 weeks of gestation. Parathyroid adenomas were detected in 81.2% of cases, hyperplasia in 6.3%, and carcinoma in 12.5%. Only one case failed surgical therapy. The postoperative incidence of clinically significant complications from the surgery was as low as 5.9% in fetuses and 0% in mothers. The incidence of clinically significant complications resulting from delayed diagnosis or postponed surgery ranged from 17.6% to 23.5% in fetuses and 18.8% to 25.0% in mothers. Postoperative hypocalcemia was detected in 62.5% of mothers and 17.6% of their newborns. All cases were easily treated with calcium replacement. Preeclampsia was diagnosed in 25% of cases. No clinically significant complications have been reported between 1993 and January 2005. This review suggests that parathyroidectomy performed in the third trimester of pregnancy is effective and has less risk than previously reported. Postponing surgery may be hazardous. Postoperative hypocalcemia is common but easily treated. Hyperparathyroidism should be considered a risk factor for preeclampsia. Target Audience: Obstetricians & Gynecologists, Family Physicians. Learning Objectives: After completion of this article, the reader should be able to summarize the maternal and fetal complications of a delayed diagnosis and/or postponed surgery, recall that surgery of a parathyroid tumor can be safely performed in the third trimester, and describe pregnancy complications of hyperparathyroidism.

Sexual Dysfunction, Depression, and Anxiety Among Patients of an Inner-City Menopause Clinic

OBJECTIVE The objective of this study was to identify the prevalence of female sexual dysfunction (FSD) in a sample comprising women of mostly Hispanic descent and low socioeconomic status (SES). METHODS Demographic data and symptoms related to sexuality were analyzed from 102 women who consecutively came to the Womens Life Center at Hartford Hospital (2004-2008). FSD was defined as decreased sexual desire, dyspareunia, or vaginal dryness; depression as one positive response to a validated three-question screening instrument; and anxiety as a positive response to whether the patient experiences anxiety sometimes or often. RESULTS The cohort was 52.9 ± 6.8 years of age (mean ± standard deviation [SD]) and 80.0% Hispanic, and 47.8% were unemployed. The majority (92.8%) earned <

Effects of age at first pregnancy and breast-feeding on the development of postmenopausal osteoporosis.

25,000, and most (95.8%) did not have a college degree. The prevalence of FSD was 75.6%. The prevalence of depression was 80.9% vs. 52.8% (p = 0.01) and that of anxiety was 76.6% vs. 45.7% (p = 0.01) among women with vs. without a decrease in sexual desire. The prevalence of depression was 83.3% vs. 55.9% (p = 0.03) and that of anxiety was 76.7% vs. 52.9% (p = 0.07) among women who reported dyspareunia vs. those who did not. Problems sleeping was the only variable associated with a statistically higher likelihood of FSD (odds ratio [OR] 5.57, 95% confidence interval [CI] 1.22-25.33, p = 0.03). No significant differences were seen when comparing FSD between Hispanics and non-Hispanics. CONCLUSIONS This sample of predominantly Hispanic women of low SES had a high prevalence of FSD. These data also suggest that poor sleep is significantly associated with FSD and that women of low SES with FSD may have a significantly higher prevalence of depression and anxiety.

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

Objective: Although pregnancy and breast-feeding require adequate calcium mobilization, it is not known if these affect the acquisition of a healthy peak bone mass (PBM) and, hence, postmenopausal osteoporosis (OPS). The objective of this study was to analyze previous pregnancies and/or breast-feeding and their association with OPS. Methods: After obtaining institutional review board approval, postmenopausal women (>49 y) presenting for a dual-energy x-ray absorptiometry bone density scan were invited to participate. Risk factors for OPS, including previous fractures, pregnancy information, and dual-energy x-ray absorptiometry results, were collected. OPS was defined as a T score of −2.5 or lower. Results: Data were obtained from 619 women. Of these, 49.8% were smokers, 27.2% used a bisphosphonate, 64.1% used hormone therapy, and 5.5% had used steroids. Based on PBM, ages at first pregnancy were dichotomized to younger than 27 years and 27 years or older. Women with a history of breast-feeding had a lower prevalence of OPS (7.6%) versus women who had never breast-fed (18.7%; P < 0.001). Women with a first pregnancy when they were 27 years or older and a history of breast-feeding had the lowest prevalence of OPS (4.6%) versus women with a first pregnancy when they were younger than 27 years and no history of breast-feeding (16.3%; P = 0.001). Conclusions: Breast-feeding seems to significantly decrease the incidence of postmenopausal OPS. Women whose first pregnancy occurs after PBM (≥27 y of age) and who have a history of breast-feeding had the lowest prevalence of OPS. Thus, an association between OPS and both breast-feeding and age of pregnancy seems to be present.

Lack of adherence to practice guidelines for women with atypical glandular cells on cervical cytology.

ObjectiveThe objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. MethodsThe parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women’s Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. ResultsThere was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46–mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). ConclusionsSupplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

The association of breast arterial calcification and coronary heart disease.

OBJECTIVE: We sought to estimate the rates and types of evaluation in women with atypical glandular cells of undetermined significance (AGC-US) on cervical cytology and to assess these findings on the basis of published management guidelines. METHODS: The rates of histologic sampling, comprehensive initial evaluations, and secondary evaluations were assessed in 477 women with an AGC-US Pap test from 1998 to 2001. A comprehensive evaluation was defined as a colposcopy and an endocervical curettage with or without a cervical biopsy. For women aged 35 or older, a comprehensive evaluation also included an endometrial biopsy. A secondary evaluation consisted of a diagnostic cone biopsy. RESULTS: Sixty-four percent of women with an AGC-US Pap test had histologic sampling; 36% were followed by repeat Pap test only. Thirty-six percent of women with an AGC-US Pap test had a comprehensive evaluation. Women with an AGC-US Pap test that was subclassified as malignant-appearing had higher rates of histologic and comprehensive evaluations than women with a benign-appearing or unspecified AGC-US Pap test (P < .01). Twenty-eight percent of women aged 35 or older had comprehensive evaluations compared with 57% of women younger than the age of 35 (P < .01). Secondary evaluations were performed in 8% of women with persistent AGC-US Pap tests and 2% of women with malignant-appearing AGC-US Pap tests after negative initial histologic evaluations. Twelve of the 42 cases of disease (29%) were diagnosed more than 1 year from the initial AGC-US Pap test. CONCLUSION: On the basis of accepted management guidelines, these data suggest that women with AGC-US Pap tests are undermanaged in both their initial and secondary evaluations. LEVEL OF EVIDENCE: III

Why the product labeling for low-dose vaginal estrogen should be changed

OBJECTIVE: To estimate whether mammography can be an early, valid tool for predicting the development of coronary heart disease (CHD) in women. METHODS: Women presenting for routine mammograms between June and August 2004 were recruited for the study. Baseline data collected included risk factors and family history of heart disease, as well as any cardiac events experienced by the patient. Similar follow-up data were collected during subsequent years, and these patient-completed surveys were correlated with the baseline mammograms screened for breast arterial calcifications. RESULTS: Throughout the 5-year follow-up, CHD was present in 20.8% of women who screened positive for breast arterial calcification and in 5.4% of who screened negative for breast arterial calcification (P<.001). Among women who did not have CHD at baseline, breast arterial calcification-positive women were more likely to develop CHD or a stroke than those who were breast arterial calcification-negative (6.3% compared with 2.3%, P=.003; and 58.3% compared with 13.3%, P<.001), respectively. These results remained significant even when controlling for age. CONCLUSION: The presence of breast arterial calcifications on mammograms indicates a significantly increased risk of developing CHD or a stroke. These results suggest that breast arterial calcifications should be routinely reported on mammograms and viewed as a marker for the development of CHD. LEVEL OF EVIDENCE: II