Biomedical subjects
Publications and source records attributed to V A Ravnikar.
This article reviews the major reasons for hysterectomies and critiques some of the alternative practices, such as medical therapy to shrink fibroids, and new surgical techniques, such as laparoscopic-assisted hysterectomies. Perhaps in response to the increased attention and the new procedures and drugs that allow more conservative management, the rate of hysterectomies has actually decreased.
We evaluated the influence of dietary, anthropomorphic, and hormonal factors on bone density in a cross-sectional sample of 281 pre- and perimenopausal women age 50-60 years living in Massachusetts. The sample included only women who had intact ovaries and were not currently using estrogen. Information on diet was obtained through a semiquantitative food frequency questionnaire. We measured bone density using single-photon absorptiometry in the non-dominant arm in two sites: the midshaft and the ultradistal radius. We observed no important associations between midshaft bone density and dietary variables but found linear relations between ultradistal radius bone density and body mass index [b = 1.10 gm/cm2 per kg/m2, standard error (SE) = 0.56], follicle-stimulating hormone (FSH) (b = -0.36 gm/cm2 per IU/liter, SE = 0.15), and several nutrients: calcium (b = 0.012 gm/cm2 per mg/day, SE = 0.007), retinol (b = 0.002 gm/cm2 per IU/day, SE = 0.0008), vitamin C (b = 0.025 gm/cm2 per mg/day, SE = 0.013), and vitamin D (b = 0.040 gm/cm2 per IU/day, SE = 0.018). We could not clearly distinguish the independent contribution of these micronutrients, however, because many were commonly ingested together in the form of supplements. Caffeine was inversely associated with bone density (b = -0.035, SE = 0.017) independent of dietary, anthropometric, and hormonal factors. Analyses of individual caffeinated beverages revealed consistent inverse associations for coffee (b = -3.42 gm/cm2 per cups/day, SE = 1.49), tea (b = -2.85 gm/cm2 per cups/day, SE = 1.56), and caffeinated cola (b = -14.0 gm/cm2 per cans/day, SE = 5.1), but not for decaffeinated coffee or decaffeinated cola [corrected]. [ABSTRACT TRUNCATED AT 250 WORDS)
This article reviewed conservative measures in dealing with issues of osteoporosis and cardiovascular disease prevention. The scientific evidence for each singular intervention is difficult to extract because there are so many confounding parameters. Moreover, improvement in nutrition and diet has its greatest impact on premenopausal women. Needless to say, a total health care approach is still beneficial: exercise, a low-fat and normocalcemic diet, and proper use of ERT. These issues need to be a concern for both the pre- and postmenopausal woman. Gynecologists as primary health care providers need to incorporate this knowledge into their practices. They should clearly understand both the benefits and shortcomings of a nutritional and exercise approach in osteoporosis and cardiovascular disease prophylaxis. In using this knowledge premenopausally, they can better prepare women for the menopause.
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A retrospective study of radiologic findings from 50 postmenopausal women who underwent hormone replacement therapy was performed to determine the frequency and distribution of changes in the screen-film mammographic appearance of breast tissue between pretreatment and posttreatment mammography. Twelve (24%) of the women developed increased parenchymal density during a median follow-up of 18 months (range, 6-39 months). Mammographic changes included diffuse increase in density in seven (14%) of the women; increased multifocal, asymmetric densities in two (4%); and cyst formation in three (6%). A greater percentage of women who received estrogen-progesterone replacement (26%, 10 of 38) demonstrated changes than those who received estrogen alone (17%, two of 12), but the difference was not statistically significant. The authors conclude that benign increases in mammographic density associated with postmenopausal hormone replacement therapy are not uncommon, and they suggest that the serial changes observed in some women may diminish the sensitivity of mammography for the earlier detection of breast cancer.
An IVF patient who was placed on leuprolide therapy prior to ovulation induction to improve ovarian response developed moderate ovarian hyperstimulation from the sole use of the GnRH agonist. Clinicians should be aware of this possible outcome.
The presence of other organ-specific autoimmune disorders in some patients with premature menopause has supported the concept of an autoimmune etiology. The authors analyzed the peripheral blood of 23 women with the diagnosis of premature menopause to detect the presence of monoclonal antibody-defined T-lymphocyte abnormalities and/or antiovarian antibodies. All subjects were less than 40 years of age with the duration of menopause ranging from less than 1 year to 11 years at the time of study. Thirty-five percent of the subjects had an elevated percentage of Ia+ (Dr-activated) T cells using monoclonal antibody L243. The percent T4 (helper) T8 (suppressor/cytotoxic) T cells and T4/T8 ratio were normal in the study group. Four subjects (approximately 17%) had elevated percentages of the age-related 3G5+ T cell subset. Two of the subjects with increased 3G5+ T cells also exhibited increased Ia+ T cells. Antiovarian steroid cell antibodies and antiadrenal cortical antibodies were present in approximately 9% of subjects. Anti-islet cell antibodies were not present. Thyroid antimicrosomal antibodies were present in 17% of subjects. Study subjects exhibited immunologic abnormalities that the authors hypothesize may play a role in the development of premature menopause in a larger percentage of patients than was previously suspected.
The purpose of this study was to examine the effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation (COH) in an in vitro fertilization (IVF) program. Patients were divided into two groups: group 1 (n = 21) had cysts with mean diameters between 10 and 45 mm on their baseline ultrasound before COH, and group 2 (n = 76) had no ovarian cysts on their baseline ultrasound. There was no statistically significant difference between the groups in maximum serum estradiol, the number of follicles greater than or equal to 10 mm on the day of human chorionic gonadotropin (hCG) injection, the number of follicles greater than or equal to 15 mm on the day of hCG injection, the number of oocytes retrieved, and the number of embryos transferred. There was no difference between the groups in the cycle cancellation rate, in the pregnancy rate per cycle, or in the pregnancy rate per embryo transfer. This study suggests that small baseline ovarian cysts do not negatively impact on ovulation induction parameters or pregnancy rates in an IVF program.
A variety of nutritional factors influence the bioavailability of calcium and increase a woman's risk of osteoporosis. Eight healthy women completed an 8-week metabolic study designed to investigate the effect of nonalcoholic carbonated beverage consumption on calcium metabolism. Compared with women receiving a control diet, women consuming a diet high in nonalcoholic carbonated beverages demonstrated similar mean serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxyvitamin D3, and osteocalcin. Twenty-four-hour urine volume, creatinine clearance, calcium-creatinine ratio, and phosphorus-creatinine ratio were similar during consumption of the diet high in nonalcoholic carbonated beverages and the control diet. Twenty-four-hour cyclic adenosine monophosphate-creatinine ratio was significantly lower in women consuming the diet high in nonalcoholic carbonated beverage compared with women receiving the control diet (342 +/- 27.4 nmol/mmol vs 409 +/- 22.1 nmol/mmol). Consumption of a diet high in nonalcoholic carbonated beverages on a short-term basis does not appear to affect adversely the serum or urinary markers of calcium metabolism.
Ovulation induction was achieved in a woman with premature ovarian failure using a regimen of high-dose clomiphene citrate in combination with prednisone and oral micronized estradiol-17 beta.
The analysis of compliance with hormonal replacement therapy in postmenopausal women must take into account the physician's knowledge of and willingness to prescribe such treatment and the patient's acceptance of the risks and benefits. Studies have shown that most women receiving oral therapy take their medication only sporadically, and those who discontinue treatment usually do so because of the fear of endometrial cancer. Both physicians and patients should be made aware that the addition of progestogen can greatly lessen this risk. Estrogen therapy has been shown to offer significant benefits, notably a reduction in the incidence of osteoporosis-related fractures. Epidemiologic models can be useful in showing both physicians and patients that hormonal treatment is safe and effective. Noncompliance, stemming from side effects or the problem of forgetting to take medications, can be improved through the use of the transdermal estrogen formulation. This product has been associated with excellent tolerability; local and systemic adverse reactions have been minimal, and any problems with unscheduled bleeding or hyperplasia can be circumvented through the addition of progestogens.
The activity and electrophoretic pattern of galactose-1-phosphate uridyl transferase (transferase), a key enzyme in galactose metabolism, were analyzed in four patients with Müllerian aplasia (Rokitansky-Küster-Hauser syndrome) and their mothers. Mothers of two of the patients had genetic variations of their transferase enzymes with activities below the normal range. Affected daughters from these two mothers also had genetic variations of the transferase enzyme. In one of the patients whose Müllerian aplasia had been diagnosed 15 years previously, premature ovarian failure developed. These case reports suggest a possible association between errors of galactose metabolism, Müllerian aplasia, and premature menopause--an association that is supported by a rodent model in which female offspring of mothers fed a high-galactose diet were born with reduced oocyte numbers and delayed vaginal opening.
Morning serum steroid levels were determined in postmenopausal chronic smokers and nonsmokers. Postmenopausal smokers (n = 9) had significantly elevated levels of cortisol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone compared with nonsmokers (n = 16). The increases were most significant for cortisol (P less than 0.001) and 17-OHP (P less than 0.0005). Estrone, estradiol, dihydrotestosterone, and dehydroepiandrosterone sulfate did not differ between the groups. P to estrogen ratios tended to be higher in the smoking population. The significantly elevated P levels observed in the group of postmenopausal smokers may explain, in part, the epidemiologic finding that women smokers have a decreased incidence of endometrial carcinoma. In addition, the hypercortisolism associated with smoking may increase the risk of osteoporosis.
To further investigate the relationship between insulin and androgen secretion in hyperandrogenic women, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects. Significant positive correlations were demonstrated between fasting serum insulin concentration and both androstenedione (delta 4A) and testosterone (T) concentrations, which were independent of body mass index (kg/m2). A strong negative correlation was demonstrated between fasting insulin and dehydroepiandrosterone sulfate (DHEAS) levels within the HA group (r = -0.84, P = 0.003). Significant positive correlations were also demonstrated between the cumulative sum insulin response during OGTT and the percent change from fasting baseline to 3 hours in serum delta 4A (r = 0.65, P = 0.006), T (r = 0.51, P = 0.033), and dihydrotestosterone (DHT) concentrations (r = 0.75, P less than 0.001). Our data suggests that abnormalities in insulin secretion are common in HA women and that there is a strong correlation between changes in serum concentrations of insulin and androgens during an OGTT.
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Studied was the peripheral bone density of 39 women (ages 18 to 43) with the diagnosis of secondary amenorrhea in an effort to define the population of amenorrheic women at risk for osteoporosis. Eight women had exercise-induced amenorrhea (athletes), 20 women had amenorrhea associated with weight loss, and 11 women had premature menopause. These diagnoses were made on the basis of history, physical examination, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels, and failure to have withdrawal bleeding after the administration of progestin. Twenty-five nonathletic, normally menstruating women served as control subjects. The peripheral bone density of the amenorrheic athletes (0.738 g/cm2 +/- 0.047) was not significantly different from that of the controls (0.726 g/cm2 +/- 0.044). The average bone density of the group with weight loss-associated amenorrhea (0.672 g/cm2 +/- 0.066) was significantly less than controls (P less than .005) as was that of the women with premature menopause (0.616 g/cm2 +/- 0.048, P less than .001). There was a significant correlation between months of amenorrhea and decrease in bone density (r = 0.506, P less than .001). From this study it was concluded that women with exercise-associated amenorrhea are not at significant risk for cortical bone loss as measured by direct photon absorptiometry. Women with weight loss-associated amenorrhea and women with premature menopause are at significant risk for bone loss when compared with normal controls.