Case-control study of gestational choriocarcinoma.

A multicentered case-control study of 75 women who had had gestational choriocarcinoma was conducted to investigate the role of reproductive and fertility factors as well as other potential risk factors in the development of this disease. Control women, identified through random digit dialing, were individually matched to cases by year of pregnancy, age at pregnancy, and geographical proximity of residence. Choriocarcinoma risk was decreased significantly as body mass index increased (P for trend = 0.03). Cases reported low-calorie dieting significantly less frequently than controls [odds ratio estimate (OR) = 0.50, P = 0.05] and were significantly less likely to participate in regular exercise (OR = 0.38, P = 0.004). Compared to women with a heavy menstrual flow, those with light menstruation had significantly elevated risk (OR = 6.69, P = 0.01). Menarche after age 12 was also associated with elevated risk of this disease (OR = 2.89, P = 0.003). There were significantly more pairs of dizygotic twins born to cases and their first degree relatives than to controls (12 case families with 13 sets of twins versus 3 sets in control families, OR = 6.36, P = 0.009). Cases were more likely to have married more than once (OR = 13.0, P less than 0.001), and infrequent intercourse was a significant risk factor (OR for weekly or less often was 3.00, P = 0.04). Risk estimates for postmolar choriocarcinoma were not significantly different from those for all other cases. These observations and some descriptive features of the disease suggest that hormonal factors, specifically below normal estrogen levels, may be associated with a disruption of normal ovulation and thus predispose to choriocarcinoma.

Evidence for a hypothalamic defect in septo-optic dysplasia.

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.

Failure of L-tryptophan to stimulate prolactin secretion in man.

The effect of oral L-tryptophan (90 mg/kg BW) on prolactin secretion in eight normal women studied either in the early or late follicular phase of the menstrual cycle was compared to the effect of a placebo alone. Plasma prolactin levels were measured before and at frequent intervals over a period of 240 min after the administration of the amino acid or placebo. Plasma free L-tryptophan concentrations were determined prior to and 60 min after ingestion of the amino acid in two of the women. Despite a 25-fold increase in plasma free L-tryptophan levels following the administration of this amino acid, the prolactin response to L-tryptophan was not significantly different from a placebo.

Pulmonary resection in the management of metastases from gestational choriocarcinoma.

Case histories of five patients with pulmonary metastases from choriocarcinoma resistant to multidrug chemotherapy are presented. Thoracotomy was performed in all cases. All tumor was removed in three patients with no other site of active disease, and these patients are surviving with no evidence of recurrent disease. In one patient, the lesion could not be completely excised because of involvement of contiguous structures, and she died of progressive disease. A second patient, with liver metastases at the time of thoracotomy, also died of progressive disease. The indications for performing thoracotomy in the management of pulmonary metastases of choriocarcinoma are discussed.

Menopause and hormone replacement therapy: an overview.

This article presents an overview of the health changes that women face as they traverse menopause and the years beyond. It serves to link a series of individual articles, which follow it in this journal issue and relate to specific topics in these areas important to women's health. Indications, contraindications, and risks and benefits of hormone replacement therapy are reviewed in depth. Alternative therapies are discussed and the role of preventive health is stressed. It seems that the menopause can be a time of positive change for women, provided that they and their physicians understand and individualize their care. If there is a central theme to such management, it is the education and responsibility of both the patient and physician.

Treatment of metastatic trophoblastic disease with poor prognosis.

Fifty-one patients are presented who were treated for poor-prognosis gestational trophoblastic disease by physicians at Duke University Medical Center (Southeastern Regional Trophoblastic Disease Center) between 1968 and 1978. Disease in 72% (37 of 51 patients) is currently in remission (8 months to 10 years). Treatment was primarily by multiagent chemotherapy, with adjunctive surgery and radiation therapy in selected patients. Unsuccessful chemotherapy prior to treatment at this center, a prolonged interval from the antecedent pregnancy to treatment, and liver metastases portended a worse prognosis in these patients.

Cerebral metastatic choriocarcinoma: intensive therapy and prognosis.

Choriocarcinoma is known to be sensitive to chemotherapy. Remission rates of 70% are reported for patients with metastatic disease. The Southeastern Regional Trophoblastic Disease Center of Duke University has reviewed its experience with the treatment of cerebral metastases from choriocarcinoma. Fourteen patients were identified as having cerebral metastases from a group of more than 500 patients with gestational trophoblastic disease (GTD) other than primary hydatidiform mole. The remission rate of 50% (7/14) was achieved by vigorous, multiagent chemotherapy and combined cerebral irradiation therapy. This series of patients is reviewed with regard to diagnosis, details of multiagent chemotherapy with cerebral irradiation, complications, and survival. The key factors for successful outcome seem to be early diagnosis and vigorous therapy.

Long-term steroid therapy in patients with adrenogenital syndrome.

Fifteen years' experience with the adrenogenital syndrome at Duke University Medical Center is reviewed. Twenty-six patients were diagnosed before age 2. Of these, 20 had the salt-losing syndrome. The complications encountered and the results obtained in terms of growth, developemnt, and fertility are discussed. Delay in diagnosis and inappropriate gender assignment continue to be a problem.

Adrenal virilism due to 21-hydroxylase deficiency in the postmenarchial female.

Five new patients with postmenarchial onset of adrenal virilism related to 21-hydroxylase deficiency are presented. Diagnostic criteria are reviewed. Four pregnancies resulting in 3 term infants occurred after instigation of therapy. Eleven patients similar in clinical presentation are reviewed for comparison. Findings of value in distinguishing these two groups of patients are discussed.

Prostaglandin F2alpha levels in human ovarian plasma in pregnancy and in a case of Halban's disease.

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.

Metastatic gestational trophoblastic disease: prognostic factors in previously untreated patients.

From 1966-1982, 138 previously untreated patients with metastatic malignant gestational trophoblastic disease received primary chemotherapy at the Southeastern Regional Trophoblastic Disease Center. Fifty-six (41%) had poor-prognosis metastatic gestational trophoblastic disease, and 51 (91%) of these patients were initially treated with multiagent chemotherapy. Sustained remissions were achieved in 128 patients (93%). Patients who had metastatic involvement of more than one anatomic site, disease duration of greater than four months, antecedent nonmolar pregnancy, or clinicopathologic diagnosis of choriocarcinoma were at significantly increased risk for failure to achieve sustained remission compared with patients who lacked these clinical features. Initial human chorionic gonadotropin level and site of metastasis had no significant effect on survival in these previously untreated patients. Patients with disease duration of greater than four months who had an antecedent nonmolar pregnancy were at significantly increased risk, with only 12 of 20 (60%) surviving, versus all of 85 patients with short duration of disease and antecedent molar pregnancy, and 32 (94%) of 34 patients with other combinations of these factors (P less than .001). Initial therapy for patients with metastatic gestational trophoblastic disease should be selected on the basis of prognostic factors that predict a high probability of failure with single-agent chemotherapy alone. Patients with prolonged duration of disease and nonmolar antecedent gestation are at high risk for failure using traditional forms of methotrexate and actinomycin D-based combination chemotherapy.

Malignant potential of gestational trophoblastic disease at the extreme ages of reproductive life.

The effect of maternal age on the incidence and significance of hydatidiform mole in 2202 patients studied at the Southeastern Regional Trophoblastic Disease Center during 1978 to 1982 is analyzed. Results are compared with a contemporary control group that comprised all types of pregnancy events. A significant increase (P less than .001) in the incidence of hydatidiform mole was seen in women 15 years of age or less and 40 years of age or more. A significant decrease (P less than .001) in the incidence of hydatidiform mole was seen in women in the 20 to 29-year age group. The greatest relative risk of hydatidiform mole occurred in women 50 years of age and older (relative risk = 519). The malignant sequelae rate from hydatidiform mole was 21.7% for the entire group. The relative risk of malignant gestational trophoblastic disease was lowest among patients 15 years of age and less (13.9%) and highest in patients 50 years of age and more (37.5%), but the differences were not significant (P greater than .05). The findings of the present study are compared with the previous literature and management recommendations are made.

Choriocarcinoma following term pregnancy.

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.

Gonadotropin release in patients with androgen insensitivity. Testicular feminization syndrome.

Two siblings are presented, both with classic androgen-insensitivity syndrome (AIS). Endocrine testing was carried out and then gonadectomy was performed. Studies in these patients with AIS revealed low control serum FSH. In these patients serum FSH was not significantly suppressed by intravenous estrogen nor adequately stimulated by FSH-LH-releasing hormone but rose normally after castration. The various studies are interpreted in the light of the known kinetics of pituitary gonadotorpins and their modulation by gonadal steroids. A third sibling is also presented.

The pulmonary metastases of choriocarcinoma.

The radiographic appearance of the pulmonary metastases of choriocarcinoma and other malignancies of gestational trophoblastic origin is described. Quantitative, though not qualitative, differences from other large series in the literature are noted. These observations may more accurately reflect the experience with this disease in North America. Three basic types of metastases are described--typical, alveolar, and embolic with emphasis placed on the most common typical metastatic lesion. The possible relation of methotrexate therapy to alveolar metastases is queried. That residual pulmonary nodules in the appropriate clinical setting need not represent viable tumor is noted.

Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium.

OBJECTIVE: To test the hypothesis tha a very-low-dose regimen of vaginal estrogen would provide effective relief from atrophic vaginitis without endometrial proliferation. METHODS: Twenty postmenopausal women with symptoms, signs, and cytologic evidence of atrophic vaginitis were enrolled. Each subject was treated with 0.3 mg of conjugated estrogens, administered vaginally 3 nights per week for 6 months. We examined the following outcomes: symptoms, vaginal cellular (cytologic) maturity, endometrial histology, sonographic evaluation of endometrial thickness, Doppler measures of uterine artery blood flow, and serum levels of estrone and estradiol. Pre- and post-treatment data were compared for each subject. RESULTS: Satisfactory relief of symptoms occurred in 19 of 20 cases. Vaginal cellular maturation improved significantly with therapy (P < .01). There were no significant changes in endometrial thickness, uterine artery blood flow, or serum estrogen levels. Endometrial proliferation was observed in one case. CONCLUSIONS: Relief from atrophic vaginitis can be achieved with 0.3 mg of conjugated estrogens administered vaginally three times per week. Endometrial proliferation may occur at this low dose, albeit rarely.

Changing rates of cesarean delivery: the Duke experience, 1978-1986.

There was a steady increase in the yearly cesarean delivery rate, from 14.0 to 24.8%, between July 1, 1978 and June 30, 1986 at Duke University Medical Center; this was associated predominantly with an increase in the rate of primary cesarean deliveries. The three most frequent major diagnoses associated with primary cesarean delivery changed significantly over the study period. Fetal compromise became the most commonly associated diagnosis (from third), dystocia second (from first), and maternal disease third (from second). The categories of fetal positional abnormalities (fourth), abnormalities of placentation (fifth), and multiple pregnancy (sixth) did not change in rank. Primary cesarean delivery patients were compared with patients who delivered vaginally using odds ratios, prevalence, and population-attributable fractions. The risk factors of nulliparity, gestational age less than 37 weeks, late decelerations, and referral had the largest impact on the primary cesarean rate. Decreases in rates related to an increased tolerance of abnormalities of labor were overshadowed by the effects of increased concerns related to fetal health.

Renal metastases of gestational trophoblastic disease: a report of eight cases.

Between 1968-1984, eight women with renal metastases of gestational trophoblastic disease were treated at the Southeastern Regional Trophoblastic Disease Center. Two (1.3%) of 154 patients referred for primary therapy and six (14%) of 42 patients referred for secondary therapy of metastatic gestational trophoblastic disease had renal metastases. All eight had coexistent pulmonary metastases. Four had central nervous system and other systemic metastases. All had high-risk metastatic gestational trophoblastic disease by assessment of individual risk factors and analysis of a prognostic index score. Three women with limited systemic tumor burden are alive after receiving multiagent chemotherapy and nephrectomy.

Germ cell malignancies of the ovary.

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.

Hydatidiform mole: diagnosis, management, and long-term followup of 347 patients.

This report concerns 347 patients with primary hydatidiform moles studied during the first 6 years (1966-1972) of operation of the Southeastern Regional Trophoblastic Disease Center. Aside from a decreased incidence, molar pregnancy in the United States follows a pattern similar to that elsewhere in the world. Abnormal bleeding is the key to early diagnosis, and the frequent use of sensitive HCG assays is the key to proper followup. Twenty percent of patients with hydatidiform moles can be expected to develop subsequent malignant sequelae. Bilateral ovarian enlargement and/or a large-for-dates- uterus should alert the physician to a greater potential for this outcome. Spontaneous elimination of HCG from the circulation following moler pregnancy, as indicated by sensitive assay, would predict a benign postmolar course; no patient in the current series who once achieved undetectable levels of HCG developed malignant trophoblastic disease.