Amenorrhea: observations based on the analysis of luteinizing hormone-releasing hormone testing.
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Biomedical subjects
Publications and source records attributed to C B Hammond.
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The diagnosis and treatment of trophoblastic disease depend upon the reliable measurement of human chorionic gonadotropin (hCG) in serum or urine. The double-antibody hCG beta-subunit assay for serum hCG combines great sensitivity, specificity, and precision but requires 36 hours to yield results. This investigation sought to increase the efficiency and total assay volume capabilities of our laboratory through the development of rapid hCG assay to augment the slower beta-subunit system. Two separate rapid hCG assays were examined--a double-antibody radioimmunoassay and a radioreceptor assay. The double-antibody assay took 5 hours to complete, while the radioreceptor assay could be completed with 3 1/2 hours. One hundred serum samples from patients with trophoblastic disease were assayed for hCG in the beta-subunit radioimmunoassay and in both rapid assay systems. No differences in results produced by the rapid double-antibody and the hCG beta-subunit assays were noted; however, results from the radioreceptor assay were significantly different (p less than 0.05) from those obtained in the beta-subunit system.
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A primary "empty" sella may be associated with significant hypothalamic-pituitary dysfunction. This report characterizes the endocrinologic and radiographic findings in six patients with hyperprolactinemia (range 34.3 to 1,170 ng/ml) ultimately found to have an enlarged empty sella. Lateral skull x-ray films and thin-section tomograms were suggestive of pituitary tumors in all patients. Four patients underwent transphenoidal sellar exploration after pneumoencephalography (PEG) failed to demonstrate air within the sella. The inability of PEG to demonstrate an empty sella in two patients was explainable on the basis of an intact diaphragma sellae with previous transient intrasellar pathology responsible for the sellar enlargement. Dynamic hypothalamic-pituitary testing yielded no consistent pattern of response. These studies suggest that an empty sella: (1) may be associated with hyperprolactinemia, regardless of etiology, (2) is not diagnosable by dynamic hormonal testing, and (3) may be indistinguishable from a pituitary tumor by current radiographic techniques.
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Two groups of hypoestrogenic women are analyzed by retrospective comparisons. Patients were observed by a single group of physicians for at least five years; 301 patients were treated with replacement estrogen and 309 patients were untreated. Incidence figures for various metabolic diseases present at entry and both during and after estrogen therapy were compared by the usual statistical analysis and by statistical adjustments for certain group differences (Mantel-Haenszel statistic). The long-term administration of estrogen to these relatively young women with hypoestrogenism was associated with significantly lower rates of development of cardiovascular disease, hypertension, osteoporosis, and fractures. Detrimental effects were a higher rate of abnormal uterine bleeding and an increase in the likelihood of developing adenocarcinoma of the endometrium. Effects of estrogen preparation, dosage, method of therapy, duration of therapy, and the addition of synthetic progestins are presented.
Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years -- 301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented.
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Historically, ovarian germ cell malignancies carry a very poor prognosis. The use of surgery alone or in combination with radiation therapy does not appreciably increase survival. The combination of surgery, chemotherapy, and, in some instances, radiation therapy has accounted for an 89% two-year survival in 26 patients with germ cell malignancies of the ovary exclusive of "pure" dysgerminoma. Short-term chemotherapy appears as effective as the long-term therapy advocated by other investigators.
Two hundred and sixty-five patients with malignant trophoblastic disease were admitted to the Southeastern Trophoblastic Disease Center at Duke University Medical Center between July 1966 and June 1976. Of these 165 patients, 20 had choriocarcinoma following a term gestation with a survival rate of 60% as compared to 95% survival rate for the remaining 245 patients. Previously described risk factors of initial human chorionic gonadotropin (hCG) titer of greater than 100,000 IU/24 hr urine, duration of symptoms for more than 4 months, significant prior unsuccessful chemotherapy or cerebral or hepatic metastases identified the "poor prognosis" group. Post-term gestation "poor prognosis" patients had a significantly lower cure rate (47%), than other patients with "poor prognosis" for gestational trophoblastic disease (75%; P less than 0.05). Post-term gestation choriocarcinoma has a propensity for more extensive metastatic spread and would appear to be less responsive to conventional chemotherapy, which may be due to an altered immune response in these patients. This suggests that an antecedent term pregnancy should be added to the previously described high-risk factors for patients with malignant trophoblastic disease.
In utero diethylstilbestrol (DES) exposure has recently been associated with apparently unique abnormalities of the upper genital tract. Utilizing a standardized technique of hysterosalpingography (HSG) and a linear planimeter, the following measurements were made in a group of 13 DES-exposed women and compared with a control group of 22 women undergoing HSG during infertility investigations (mean +/- standard error: endometrial cavity area, 323.23 +/- 32.13 sq mm versus 626.56 +/- 52.75 sq mm; endometrial cavity circumference, 128.65 +/- 5.08 mm versus 140.52 +/- 5.56 mm; upper uterine segment length, 28.80 +/- 1.11 mm versus 38.03 +/- 1.81 mm; lower uterine sugment length, 36.03 +/- 4.77 mm versus 42.24 +/- 2.39 mm; intercornual distance, 36.40 +/- 2.56 mm versus 38.25 +/- 1.58 mm; internal os diameter, 3.90 +/- 0.44 mm versus 4.43 +/- 0.23 mm; widest diameter of the endocervical canal, 3.78 +/- 0.40 mm versus 9.39 +/- 0.60 mm; isthmic tubal diameter, 1.25 +/- 0.08 mm versus 1.20 +/- 0.01 mm; ampullary tubal diameter, 4.79 +/- 0.43 mm versus 4.65 +/- 0.22 mm. The endometrial cavity area, upper uterine segment, and endocervical canal measurements were significantly smaller in the DES-exposed group (P less than 0.01). The upper genital tract abnormalities observed appeared to be unlike spontaneously occurring Müllerian malformations and correlated with DES-induced cervicovaginal changes. Primary dysmenorrhea and menstrual irregularity occurred in 40% and 47%, respectively, of the DES-exposed patients.
Twenty-four women with documented endometriosis externa were treated with methyltestosterone. Twenty-one of these patients desired fertility and three conceived (one after methyltestosterone therapy alone, two after conservative operation followed by methyltestosterone treatment). Ten patients later required surgical therapy for recurrence of pain, although all but one patient had initial relief of pain (3 to 6 months after therapy). These results of therapy are contrasted to those of similar studies in the literature in which methyltestosterone and other agents were used.
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Eleven women with secondary amenorrhea associated with hyperprolactinemia were studied. Base line evaluations, visual field determinations, and routine sella turcica x-rays were normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were carried out. These studies included polytomography of the sella turcica; dynamic pituitary testing of growth hormone reserve, adrenocorticotropic hormone reserve, and gonadotropin reserve; and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are utilized. The most sensitive diagnostic indices available are (1) polytomography, (2) the magnitude of the plasma prolactin elevation, and (3) the failure to suppress prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.
A 21-year-old man demonstrated septo-optic dysplasia. Optic and retinal colobomas were present and panhypopituitarism was documented. Releasing hormone studies showed partial luteinizing hormone (LH) response and no follicle-stimulating hormone response to administration of gonadorelin (LH-releasing hormone); thyroid-stimulating hormone (TSH) and prolactin levels were increased normally after administration of protirelin (thyrotropin-releasing hormone). The LH, TSH, and prolactin responses are believed to be evidence of intact pituitary function and suggest that a hypothalamic defect accounts for the hypopituitarism.
It has been demonstrated that the ovary bearing the corpus luteum in the human is responsible for the major portion of prostaglandin F2alpha (PGF2alpha), total estrogen, and progestin production during the luteal phase of a normal menstrual cycle. This study was performed with the intent to gain more information about the secretion of PGF2alpha in conditions that prolong the life span of the corpus luteum, such as pregnancy and Halban's disease. Utilizing a specific radioimmunoassay for PGF2alpha, ovarian venous plasma levels were measured in 7 pregnant women and in a patient with Halban's disease. During the first and second trimester of pregnancy, PGF2alpha values in plasma from the active and inactive ovary were comparable and were significantly lower than concentrations in plasma from the active ovary during the luteal phase of the normal cycle. In a patient with persistent corpus luteum or Halban's disease, PGF2alpha concentrations of venous plasma from the ovary bearing the corpus luteum were significantly lower than those obtained from the contralateral ovary. These observations indirectly support the hypothesis that prostaglandins produced within the ovary may have a role in luteal regression.
Thirty-two males were treated with clomiphene citrate for a minimum of six months, a maximum of twelve months, or until pregnancy occurred. Among these patients, thirteen pregnancies occurred. Climiphene citrate appears a reasonable pharmaceutical method for management of idiopathic oligospermia.