Endometrial cancer in elderly women: A histologic and steroid receptor study.

BACKGROUND: Information on steroid receptor content in endometrial tissue of aging women is limited and somewhat controversial. The high incidence of endometrial cancer (EC) and the implication of hormone replacement therapy (HRT) in this group prompted the investigation of steroid receptors and endometrial cancer histology in the elderly. OBJECTIVE: Review of histologic characteristics correlated with estrogen and progesterone receptors (ER and PR) status in EC in women over 75 years of age in order to determine the prevalence of a more aggressive endometrial neoplasm arising in late postmenopausal atrophic endometrium of elderly patients. METHODS: Histologic slides and deeper sections stained immunohistologically for ER/PR from 54 cases of EC in women aged 75-95 years were reviewed. The histologic characteristics and degree of differentiation were correlated with the steroid receptor status, evaluated on a scale of 0-3. Benign endometrial tissue from women of the same group was used as controls. RESULTS: The 57.4% endometrioid adenocarcinomas were mostly moderately and poorly differentiated. The nonendometrioid carcinomas were anaplastic, papillary, clear cell, squamous cell, mixed müllerian and nongestational choriocarcinoma. The staining intensity for ER/PR decreased with the degree of dedifferentiation being weak or absent in nonendometrioid tumors. CONCLUSION: Elderly patients have less differentiated EC displaying histologically nonendometrioid patterns ('alienation') with no differential loss of receptors in cancer. ER/PR are partly preserved in endometrioid tumors and controls. We conclude that differential loss of receptor capacity is not a factor in pathogenesis of this age-related cancer.

Menopause-related oral alveolar bone resorption: a review of relatively unexplored consequences of estrogen deficiency.

OBJECTIVE: The alveolar processes of the maxilla and mandible provide the bony framework for tooth support. Osteoporotic changes of these bones may directly affect tooth stability and retention. This report reviews studies that have evaluated the relationship between systemic osteoporosis and oral alveolar bone mass as well as the effect of estrogen use on oral alveolar bone and tooth retention. DESIGN: Ten years (1989-1998) literature review. RESULTS: Studies reviewed demonstrate a positive correlation between systemic bone mass and systemic osteoporosis to oral bone resorption. Estrogen replacement therapy affects oral bone in a manner similar to the way it affects other sites. CONCLUSIONS: It is evident that postmenopausal estrogen users may retain more teeth after menopause. Sustained oral health and better tooth retention are potentially additional benefits for hormone replacement therapy users after menopause.

Functional anatomy and physiology of the female breast.

As mammals, we define our biologic class by the function of the breast in nourishing our young. As obstetricians, we seek to enhance or diminish function; as gynecologists, the appearance of inappropriate lactation (galactorrhea) may signify serious disease. In this article, development, differentiation, and functional anatomy of the breast is discussed. The hormonal interactions responsible for these events and the physiologic function of this vital reproductive organ during the life cycle of the woman is emphasized.

Incidence of autoimmune antibodies in failed embryo transfer cycles.

PROBLEM: The presence of antiphospholipid antibodies lupus anticoagulant (LAC), anticardiolipin antibody (ACA) as well as antinuclear antibody (ANA) has been associated with early spontaneous pregnancy loss and adverse pregnancy outcome. The purpose of this study was to investigate the possible role of autoimmune antibodies (LAC, ACA, and ANA) as a cause of implantation failure following embryo transfer (ET) after in vitro fertilization (IVF). METHOD: Three groups were studied: Group I, 56 patients who failed to conceive following ET; group II, 14 patients who have conceived following IVF-ET and delivered or are carrying an uncomplicated ongoing pregnancy; and group III, 69 patients who were new candidates for IVF-ET. RESULTS: Eighteen out of 56 (32.1%) of patients who failed to conceive following previous IVF-ET cycle (group I) tested positive for one or more of the autoimmune antibodies. None of the 14 patients of group II tested positive for autoimmune antibodies (P < .02). Seven out of the 69 patients (10%) of group III were found positive to one or more of the autoimmune factor. This rate is significantly lower than the rate of positive autoimmune antibodies detected in group I (P < .003). Fifteen patients of the 18 who tested positive for autoimmune antibodies and who had previously failed to conceive following ET underwent a subsequent IVF-ET cycle while being treated with prednisone and aspirin. Seven out of the 15 (46.6%) conceived and were able to sustain a clinical ongoing pregnancy. CONCLUSIONS: Patients receiving ET are carrying viable embryos within the intrauterine environment. Therefore, in this unique group of patients, failure to demonstrate a positive pregnancy test represents an implantation failure or a very early postimplantation loss. The results of this study suggest that periimplantation events may be affected by autoimmune antibodies. Very early miscarriage or implantation failure may be related to the same pathophysiological mechanism that causes recurrent miscarriages and is diagnosed incorrectly as infertility.

Gynecologic manifestations of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome is a chronic, inflammatory autoimmune disease in which the salivary and lacrimal glands are progressively destroyed by lymphocytes and plasma cells. Because women are affected 10 times more often than men, we studied gynecologic manifestations of Sjögren's syndrome. STUDY DESIGN: One thousand questionnaires were sent to women with Sjögren's syndrome in New York, New Jersey, Connecticut, and Pennsylvania. Five hundred thirty-nine women responded. RESULTS: Women with Sjögren's syndrome reported significant vaginal dryness. There was no relationship of Sjögren's syndrome to either the incidence of infertility or miscarriage, although the 4% incidence of congenital anomalies in offspring was relatively high. Of the congenital anomalies, nine of 19 (47%) were cardiac. A long menstrual cycle (> 35 days) was associated with infertility and neuropathy. CONCLUSIONS: The vaginal dryness in women with Sjögren's syndrome is not surprising, because the nasal and esophageal mucosae are also dry in this disorder. The relationship of infertility to a long menstrual cycle may simply indicate the presence of ovulatory dysfunction or inadequate luteal phase unrelated to Sjögren's syndrome. The relationship of neuropathy to a long menstrual cycle may be related to repeated, prolonged estrogen or progesterone exposure during the long cycles or to involvement of hypothalamic-pituitary-ovarian function.

Menopause medicine: current treatment options and trends.

Demographic trends and increasing demand, as well as the intricacy of the emerging field of menopause medicine, dictates the need for a multidisciplinary approach for the care of the peri- and postmenopausal patient. A menopausal program benefits the individual patient by obviating the acute symptoms and by preventing long-term consequences. As morbidity and mortality rates associated with the long-term implications are reduced, substantial public health aspects are also beneficially affected. Cost effectiveness of a menopause program and routine HRT should be calculated as the net present value (NPV) for the health care financing program, and should prove to be greater than the NPV of future costs anticipated without an investment in primary preventive menopause program. We believe that the educated use of a menopause counseling program will yield an increasing benefit for the individual patient and the community. Should menopause be regarded as an endocrinopathy, thus justifying routine HRT, or are we engaged in the "medicalization" of a physiologic process? Bearing in mind the data reviewed above, it seems to us that ample reason exists to make every woman aware of the opportunity to receive long-term HRT. The decision to use it depends heavily on the patient's own informed assessment of her particular benefit-risk equation. Combined-continuous estrogen-gestagen replacement seems to provide the desired multisystem beneficial effects, and at the same time be the most convenient and associated with the least short-term side effects. Although emerging trends regarding the long-term risks associated with the use of such regimes are reassuring, more information needs to be elaborated before final conclusions can be offered.

Diagnosis and management of perimenopausal and postmenopausal bleeding.

The menopausal years are characterized by a deficiency of progesterone and relative hyperestrogenism. This hormonal imbalance creates an environment favorable for the development of endometrial hyperplasia. The pathologic progression of hyperplasia to endometrial carcinoma can be arrested with progestogen therapy. A simple diagnostic approach for peri- and postmenopausal bleeding disorders is presented, along with a rational treatment regimen. Some of the risks and benefits of hormonal replacement therapy are discussed.

The neuroendocrinology of amenorrhea.

Hypothalamic amenorrhea has a pathophysiologic basis. Loss of gonadotropin-releasing-hormone (GnRH) pulse amplitude and frequency is the proximal event in the evolution of hypogonadotropic hypogonadal amenorrhea. Except for rare conditions in which the parenchymal source of GnRH is destroyed, the major cause of dysfunction in GnRH is thought to be related to abnormalities of the neurotransmitters that control GnRH synthesis, storage and timely discharge. The dopamine/norepinephrine and endorphin systems are the principal targets of current research. This new knowledge should have a major impact on physicians' thinking about hypothalamic amenorrhea. A spectrum of clinically recognizable disorders appears in conjunction with alterations in GnRH secretions. Temperature control, appetite, fluid volume and behavioral distortions are now understandable as expressions of expanding hypothalamic dysfunction.

The microenvironment of the ovarian follicle.

Observations on the steroid and peptide concentrations and interactions in the microenvironment of the human ovarian follicle have led to an understanding of three important issues in reproductive biology: (1) how the oocyte-granulosa-cell complex matures, (2) how a single follicle is selected and prepared for ovulation and (3) how the events are synchronized so that an ovum ready for fertilization is extruded at ovulation. These findings have clinical significance.

A practical approach for the evaluation of women with abnormal polytomography or elevated prolactin levels.

Based upon the experience gained in the evaluation of 60 patients with abnormal polytomography and/or elevated prolactin levels, the following observations can be made: Patients with amenorrhea, amenorrhea and galactorrhea, galactorrhea alone, or anovulatory cycles and infertility may or may not have pituitary tumors. Clinical symptoms do not always correlate with the prolactin level, and patients with normal prolactins may have pituitary tumors. The incidence of empty sella is significant (15.8% in this series). Visual field examination is not a useful screening procedure, but evaluation of thyroid function is important to detect the occasional patient with hypothyroidism (3.5% in this series). The insulin tolerance test is not helpful in detecting the presence of pituitary tumors or in guiding management decisions, and the CT scan contributes little and should be omitted from the evaluation process. A straightforward, economical, and efficient approach to this clinical problem is presented.

Plasma estradiol window and urinary estriol glucuronide determinations for monitoring menotropin induction of ovulation.

The plasma estradiol response is maximal 8--10 hours following mentropin injection. To obtain closer control, a menotropin protocol using 5 PM--8 PM injections and 8 AM blood sampling with a plasma estradiol window of 1000--2000 pg/ml was evaluated with simultaneous calibration of a urinary estriol glucuronide radioimmunoassay. One hundred twenty-eight paired urine and plasma samples were assayed in 48 cycles. In 26 cycles with paired samples on the day of human chorionic gonadotropin (hCG) injection, there were no cases of severe hyperstimulation, 2 cases of moderate hyperstimulation, and 11 pregnancies (42% of cycles given hCG). A window of between 40 and 100 micrograms/day of urinary estriol glucuronide corresponded to the 1000--2000 pg/ml plasma estradiol window by regression analysis. The pregnancy and hyperstimulation rates were compared with those observed in protocols previously published. Radioimmunoassay of urinary estriol glucuronide is faster and simpler than radioimmunoassay of plasma estradiol.

Ovulation and pregnancy rates with clomiphene citrate.

A review of recent experience with clomiphene citrate at the Yale-New Haven Medical Center yields the following conclusions: 1) Clomiphene citrate administered at high doses (150 mg and 200 mg) is effective in inducing ovulation in women who would otherwise have failed to conceive if treatment were restricted to only lower dosage regimens. 2) Therapy with clomiphene citrate should be initiated with the 50-mg dose. The 100-mg dose should be reserved for those who fail with the lower dose. 3) Children resulting from clomiphene-induced ovulations appear to be developing normally both mentally and physically. Congenital malformations found in children from clomiphene-induced pregnancies are those seen commonly in general obstetric practice resulting in no significant problems for the children. 4) After 3 ovulations with clomiphene citrate approximately 50% of the patients can be expected to conceive. A 50% conception rate after 3 ovulations with clomiphene citrate does not represent a discrepancy between ovulation rates and pregnancy results, for it agrees statistically with the results obtained for the general population.