Stanley Deutsch

Plasma levels of fractionated estrogens and pituitary hormones in endometrial carcinoma

Plasma levels of estrone (E1), estradiol-17beta (E2), and estriol (E3), as well as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured in 30 control subjects and in 20 postmenopausal patients with adenocarcinoma of the endometrium. Within the sensitivity of the assay (5 to 10 pg.), no E3 was found. Mean levels of E1 and E2 in the patients with carcinoma (42.64+/-3.8 (S.E.M.) and 17.3+/-1.7 (S.E.M.) pg. per mililiter) were significantly higher than those measured in the control subjects (E1=26.97+/-2.4 (S.E.M.) pg. per mililiter, p less than 0.001; E2=12.08+/-1.2 (S.E.M.) pg. per milliliter, p less than 0.02). Effects of age, diabetic status, and obesity were taken into consideration. Significant differences in FSH and marginally significant differences in prolactin levels were observed between the two groups. Mean levels of FSH, LH, and prolactin in the control group and the group with adenocarcinoma, respectively, were as follows: FSH=152.3+/-7.0 (S.E.M.) versus 98.1+/-8.9 (S.E.M.) mI.U. per milliliter, p less than 0.001; LH=64.7+/-3.1 (S.E.M.) versus 66.5+/-5.2 mI.U. per milliliter, difference not significant; and prolactin=14.3+/-0.9 (S.E.M.) versus 17.8+/1.7 (S.E.M.) ng. per milliliter, p less than 0.06. These results, as well as previously reported alterations in human growth hormone secretion, suggest aberrations in hypothalamic function in endometrial carcinoma.

The correlation of serum estrogens and androgens with bone density in the late postmenopause

A pilot group of 16 women in the late postmenopause were evaluated for bone density by computerized axial tomography (CT) scanning and for hormonal milieu. A highly statistically significant positive correlation between lumbar‐3 spongiosum density and both dehydroepiandrosterone‐sulfate (DHEA‐S), r = 0.67; P < 0.005 and androstenedione (A), r = 0.56; P < 0.03 was found. No such correlations were observed with estradiol (E2), estrone (E1) or an array of other hormones. The results of this preliminary report indicate a clear association of weak androgens with bone density in the late postmenopause.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

Comparison between degree of systemic absorption of vaginally and orally administered estrogens at different dose levels in postmenopausal women

This report compares factors involved in routes of administration of estrogens for treatment of menopausal symptoms. The following factors were compared in regimens of topical vaginal estrogen administration and oral administration: varying dosages of estrogens were administered and a comparison was made of the systemic absorption at each dosage level by both oral and vaginal routes. The study design mimicked the clinical longer-term use of these compounds instead of an acute single dose administration. 46 postmenopausal patients of comparable age and medical status were studied. Estrogen therapy in these subjects was indicated because of vasomotor symptoms or vaginal problems such as dyspareunia. Patients were given a regimen of a conjugated estrogen (Premarin) .3 .625 or 1.25 mg either orally or vaginally daily. Blood was drawn daily for radioimmunoassay of total plasma estrogen levels. Vaginally administered medication for each dose level studied resulted in significantly lesser increases in blood estrogen values as compared to those produced by the same dose given orally. Of greatest clinical significance was the finding that after a weeks therapy with .3 mg vaginally there was no systemic absorption. Relief of vaginal symptoms and a change from an atrophic vaginal cytologic smear to a greater than 70% superficial cell count were achieved in every topically administered case. A daily vaginal dose level of .3 mg was sufficient.

Effect of advancing pregnancy on the glucose tolerance test and on the 50-g oral glucose load screening test for gestational diabetes.

&NA; To determine the validity of the 50‐g, one‐hour glucose screening test for gestational diabetes in relation to the duration of pregnancy, 101 patients from a high‐risk population had the screening test in the first trimester and glucose tolerance tests (GTT) in the second and third trimesters. The sensitivity (88%) and specificity (82%) of the screening test were similar to values reported when the test is performed later in pregnancy. However, immediate follow‐up GTTs in the second trimester revealed only 25% instead of 88% of the gestational diabetic patients uncovered by the positive screening tests. Guidelines for screening for gestational diabetes should include follow‐up with a third‐trimester GTT on all patients who have positive screening tests even in the presence of normal follow‐up second trimester GTTs. (Obstet Gynecol 68:362, 1986)

Effect of Gemfibrozil on Serum Lipids in Man

The effect of gemfibrozil, a new lipid-lowering agent, was studied in 22 patients. Each patient served as his own control in a double blind study. The administration of gemfibrozil, for a period of 24 months, 1200 mg daily, reduced mean serum triglyceride levels by 45.6% (p<0.001) and mean serum cholesterol levels by 8.3% (p<0.001). Mean serum HDL cholesterol was increased by 32.3% (p<.0001) and mean serum LDL cholesterol levels were decreased by 11.4% (p<0.01). Mean serum VLDL cholesterol was decreased by 45.9% (p<0.001). A 3-hour glucose-tolerance test was done in each patient during a placebo-control period and during the administration of gemfibrozil. Mean plasma glucose was moderately increased during the administration of gemfibrozil at all points on the glucose tolerance curve, and to levels of significance at one (p<0.05) and two hours (p<0.02). There was no effect of the drug on serum immunoreactive insulin. No subjective side effects were apparent.

Excessive estradiol secretion in polycystic ovarian disease

Polycystic ovarian disease is both a hyperestrogenic and a hyperandrogenic syndrome, and all studies have shown that hyperestrogenemia is the result of an elevation of estrone with plasma estradiol levels in the normal follicular range. Because a literature search failed to reveal any report of polycystic ovarian disease with significantly elevated estradiol levels, we report a case in which the plasma estradiol was so massively elevated as to mimic an estrogen-producing neoplasm. This case also suggests that although polycystic ovarian disease is a very rare cause of such excessive estradiol production, it should be included in the differential diagnosis of estrogen-producing neoplasms.

Comparison of the adrenocorticotropic hormone stimulation test with and without prior dexamethasone suppression in the diagnosis of congenital adrenal hyperplasia

A comparison was made of the ACTH stimulation test with and without prior dexamethasone suppression in 10 patients, each of whom served as her own control. It was found that it is not necessary to administer DEX before the test, the specificity and sensitivity of both tests being the same in the diagnosis of CAH, although the calculated values are lower when DEX is given. Further investigation with HLA typing and ACTH stimulation testing is necessary to establish whether either or both types of ACTH stimulation tests are capable of discriminating between the heterozygotic and homozygotic varieties of CAH.

Hormone production by the postmenopausal ovary in cases of benign ovarian neoplasia

OBJECTIVE The objective of this study was to determine whether hormone production by postmenopausal ovaries containing benign ovarian tumors differed from that of normal postmenopausal ovaries. STUDY DESIGN The sera of 32 postmenopausal patients were assayed before and after bilateral oophorectomy for estrone, 17 beta-estradiol, androstenedione, testosterone, and dehydroepiandrosterone sulfate. The data from all patients as a group were analyzed, followed by analysis of the data from 15 patients with normal ovaries separately from the remaining 17 patients who had nonfunctioning, benign ovarian tumors. RESULTS For patients with benign ovarian tumors there was a statistically significant drop in estrone (from a presurgical level of 55.8 +/- 46.3 pg/ml to a postoperative level of 29.9 +/- 10.2 pg/ml, p < 0.03) and 17 beta-estradiol (from 18.6 +/- 14.1 pg/ml preoperatively to 9.8 +/- 3.8 pg/ml postoperatively, p < 0.02). For postmenopausal woman with normal ovaries there was no significant drop in estrone or 17 beta-estradiol after bilateral oophorectomy. There was a statistically significant drop in testosterone and androstenedione after bilateral oophorectomy both for women with normal ovaries and for those with benign tumors. No significant differences in dehydroepiandrosterone sulfate were noted in either group. CONCLUSIONS These data suggest that, although normal postmenopausal ovaries have not been demonstrated to secrete clinically significant amounts of estrogen, those that contain benign ovarian tumors do secrete small but significant amounts of estrone and 17 beta-estradiol. Both tumor-containing and normal ovaries secrete the androgens androstenedione and testosterone, this secretion not being significantly influenced by the presence of a tumor.

Immunoreactive Plasma Estrogens and Vaginal Hormone Cytology in Postmenopausal Women

The vaginal hormone cytology and the serum estrogen levels (as determined by radioimmunoassay) of 39 post-menopausal patients were compared. All cytologic parameters showed high statistical correlations with radioimmunoassay values, but these general associations could not be applied to individual patients. A more detailed analysis showed that an atrophic smear (eg, karyopyknotic index [KI], < 10%; parabasal level, > 20%; maturation value [MV], < 40%) indicate estrogen deficiency in the postmenopause. When the KI is 20%-40%, the parabasal cells less than 20% or the MV 40%-60%, the evaluation of estrogen status, on the basis of hormone cytology alone, is indeterminate. The three cytologic indices studied seem much more useful for detecting estrogen deficiency than estrogen excess in the postmenopause. The fact that immunochemical characteristics are not always related to biologic behavior must also be considered when interpreting these findings.