Adherence to screening guidelines for breast and cervical cancer in postmenopausal women with coronary heart disease: an ancillary study of volunteers for hers.

Postmenopausal women with coronary heart disease (CHD) who volunteered for the Heart and Estrogen/Progestin Replacement Study (HERS) randomized clinical trial had high rates of gynecological abnormalities. We examined compliance with gynecological cancer screening and factors affecting this behavior. Women who met inclusion criteria for HERS and were seen for screening by the study gynecologist were considered eligible for this study. Data were abstracted from study records, and additional information was obtained by telephone questionnaire. Adherence to mammography, breast examination, pelvic examination, and Pap smear recommendations was assessed. Provider behavior and its effect on compliance were assessed. Compliance rates were 59.1% for monthly breast self-examination (BSE), 67.2% for yearly mammography, 73% for yearly Pap smear and pelvic examination, and 75.7% for provider breast examination. Over 50% of patients had most of their screening tests done within the last year. Provider behavior was significantly related to patient screening compliance for mammography, breast examination, Pap smear, and pelvic examination. Provider gender was not significantly related to adherence. There were no significant differences in compliance rates based on the type of most recent coronary event. Compliance rates did not differ significantly between patients with and without gynecological abnormalities, except for mammography (78.3% versus 48.3%, p = 0.02). The majority of patients were compliant with gynecological screening. Among patients with gynecological abnormalities, mammography compliance was significantly lower. Provider behavior was an important factor in influencing women to obtain preventive screening. There were no significant differences in compliance based on provider gender or type of coronary event preceding HERS enrollment.

Estradiol as an antioxidant: incompatible with its physiological concentrations and function.

Estradiol has been documented to inhibit the oxidation of low density lipoprotein (LDL). We show that physiological concentrations of estradiol do not inhibit the oxidation of LDL by copper. LDL samples isolated from a) premenopausal and postmenopausal women and from b) women at different time periods during their menstrual cycle, who differ vastly in plasma estradiol levels, were also oxidized at the same rates by copper. In contrast, LDL samples isolated from c) women who were hyperstimulated during in vitro fertilization (IVF), with estradiol concentrations above 2000 pg/ml, were resistant to oxidation by copper. However, these LDL samples were also oxidized at a higher rate by peroxidases. More importantly, subjects with high estradiol levels also showed an increase in myeloperoxidase (MPO) protein in the plasma. Based on these results, we conclude that at physiologic concentrations, it is unlikely that estradiol could act as an antioxidant. In fact, the ability of estradiol to induce MPO and become a prooxidant might instead suggest that MPO-mediated oxidative clearance of LDL from plasma by liver might favorably influence the outcome of atherosclerosis.

RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri.

More than a decade after the serendipidous discovery of RU486, numerous antiprogestins have been synthesized and studied. Interest in how antiprogestins exert their antagonist effect has led to novel information about the molecular mechanisms of progesterone action. The pivotal role that progesterone plays in reproductive biology has led to research in many areas where a potential role for these compounds may be found in health and disease. RU486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Uterine leiomyomata show a significant reduction in size after administration of RU486 for 3 months. Although much research remains to be carried out, RU486 appears promising as alternative therapies for these diseases.

PIP: More than a decade after the discovery of RU-486, numerous antiprogestins have been synthesized. Interest in the antagonist effect of antiprogestins has revealed novel information about the molecular mechanisms of progesterone action owing to the pivotal role that progesterone plays in reproductive biology. RU-486 side effects include hot flashes and transient increases in liver transaminases. Generalized cystic changes in the endometrium have been demonstrated consistent with a chronic unopposed estrogen effect. RU-486 has been shown to relieve pelvic pain associated with endometriosis and to decrease American Fertility Society endometriosis scores. Since uterine leiomyomas appear to be ovarian steroid dependent, it was attempted to reduce the growth of uterine fibroids by using low-dose (50 mg/day or approximately 1 mg/kg/day) RU-486 for 3 months in 10 patients. 10 patients were studied at a 25 mg daily dose for 3 months and 7 patients received 5 mg daily for the same length of time. Additionally, leiomyomata and myometrium of 5 patients treated with 50 mg daily of RU-486 and 5 untreated patients in the follicular phase of the cycle were examined immunohistochemically using antibodies recognizing estrogen receptor protein and progesterone receptor protein. Myoma size decreased approximately 22% at 4 weeks, 39% at 8 weeks, and 40% at 12 weeks. It has been shown, for the first time, that an antiprogesterone which induces acyclicity also induces a decrease in size of leiomyomata. Additionally, a small randomized study attests to the probable efficacy of RU-486 in the treatment of leiomyomata. This decrease in size is seen in the face of follicular phase levels of estrogen, and data suggest that the decrease may be mediated through its antiprogestin properties. RU-486 appears promising as a safe and well-tolerated alternative therapy for these diseases. Further investigation of the endometrial effects of RU-486 must be conducted if RU-486 is to be used for longer than 3-6 months.

Granular cell tumors of the vulva.

Granular cell tumor (GCT), although nearly ubiquitous, is seen infrequently in the vulva. A review of the surgical pathology files from Grady Memorial Hospital, Atlanta, Georgia, from 1983 through 1987 identified eight cases of vulvar GCT. Five of the eight patients had more than one skin and soft tissue lesion. Two of the five had biopsy-proven multicentric GCT with a unique clinical course. One of the patients was a 32-year-old woman with multiple vulvar, lingual, laryngeal, bronchial and pulmonary GCT, necessitating multiple excisions and ultimately pneumonectomy. The second patient had multiple GCTs in the vulva and inguinal area and finally in both lungs, resulting in her death at age 39. No dependable microscopic features could be identified to distinguish benign GCT from its more aggressive variant. However, Feulgen DNA histomorphometry demonstrated aneuploidy in the patient with apparent lung metastases, whereas the tumors from patients with a benign course as well as from the patient with multiorgan involvement were diploid. In three of five patients who could be interviewed there was a history of soft tissue tumors in members of the family. The multifocal nature and possible familial component of GCT need to be explored further.