Charles B. Hammond

Effects of long-term estrogen replacement therapy

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.

Treatment of metastatic trophoblastic disease: Good and poor prognosis

Abstract This study reports results of therapy in 91 patients with metastatic gestational trophoblastic disease treated by physicians of the Southeastern Regional Trophoblastic Disease Center. The 91 patients were grouped into good (79 per cent) or poor (19 per cent) prognostic categories. “Poor prognosis” patients were identified by the presence of an initial pretreatment human chorionic gonadotropin (HCG) titer greater than 100,000 I.U. per 24 hours, duration of disease greater than 4 months, or the documentation of cerebral or hepatic metastases. The patients with “good prognosis” metastatic disease were all treated with systemic single agent chemotherapy with methotrexate or actinomycin D. Seventy of these 71 patients were cured. The poor prognosis patients were treated by two treatment protocols. The earlier group of 7 patients in this category were treated with combination chemotherapy only after resistance to conventional single agent methotrexate and actinomycin D had failed to cure the patient. Only one patient surviced. The later group of 10 patients with “poor prognosis” disease were initially treated with combination chemotherapy and 7 were cured. The roles of hysterectomy with chemotherapy, simultaneous liver and/or hepatic irradiation with chemotherapy, and arterially infused chemotherapy are discussed.

Effects of long-term estrogen replacement therapy: II. Neoplasia☆

Abstract 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.

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 womens 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.

Diethylstilbestrol-Induced Upper Genital Tract Abnormalities*

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.

Treatment of nonmetastatic gestational trophoblastic disease: Results of methotrexate alone versus methotrexate-folinic acid

Two treatment regimens for nonmetastatic gestational trophoblastic disease are compared in this retrospective study. The course of 39 patients with nonmetastatic gestational trophoblastic disease treated with methotrexate alone is contrasted to that of 29 patients with nonmetastatic gestational trophoblastic disease who were treated with methotrexate alternated with folinic acid. Of those patients initially treated with methotrexate alone, 7.7% developed methotrexate-resistant disease and required a change in chemotherapy for induction of remission. In contrast, 27.5% of patients initially treated with methotrexate and folinic acid developed methotrexate-resistant disease and required a change in chemotherapy to achieve remission. Ultimately, remission was achieved in all patients. Methotrexate as single-agent chemotherapy was found to be consistently more toxic than methotrexate alternated with folinic acid. It is concluded that methotrexate with folinic acid at the dosage used in this study, while less toxic than methotrexate alone, is less effective than methotrexate alone in the induction of remission of nonmetastatic gestational trophoblastic disease.

The Diagnosis and Therapy of Luteal Phase Deficiency

Between 1973 and 1975, 16 patients evaluated for infertility at Duke University Medical Center were diagnosed as having luteal phase deficiency. A majority had had prior infertility surveys, and the average duration of their infertility exceeded 2 years. The diagnosis was suspected after study of basal body temperature charts and menstrual patterns in more than 80% of the patients. This diagnosis was established by timed endometrial biopsy. The primary method of therapy was supplementation of the luteal phase with progesterone vaginal suppositories. The pregnancy rate after therapy was 50% and pregnancy occurred after a mean of five treatment cycles. The minimal follow-up of patients who failed to conceive was 8 months. To date, the majority of these pregnancies have been completed without complication and the remainder are progressing satisfactorily. Two additional patients developed luteal phase deficiency while taking clomiphene citrate and became pregnant with progesterone supplementation.

role of Computed Axial Tomography of the Chest in Staging Patients With Nonmetastatic Gestational Trophoblastic Disease

&NA; Thirty‐nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x‐ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexatefolinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P < .006). All patients who failed methotrexate‐folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life‐threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x‐ray are predictive of an increased risk of methotrexate‐folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate‐folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease. (Obstet Gynecol 68:348, 1986)

Ovulation induction with pulsatile gonadotropin-releasing hormone administration in patients with polycystic ovarian syndrome

Gonadotropin-releasing hormone (0.025 microgram/kg) was administered intravenously in a pulsatile fashion to four subjects with polycystic ovary syndrome for a total of six cycles. Five of the six cycles culminated in ovulation, although in one course the response occurred too early to be attributed to the therapy alone. No pregnancies resulted. All luteal phases were of normal duration, but progesterone production as manifested by serum progesterone determination was deficient in some. If additional investigation confirms these preliminary findings, this form of therapy may offer a safe and economic alternative for anovulatory patients refractory to clomiphene citrate therapy. The response of the four subjects suggests that pulsatile gonadotropin-releasing hormone administration may override hypothalamic-pituitary dysfunction and result in ovulatory menstrual cycles.

Estrogen replacement therapy.

The popularity of estrogen therapy for the menopausal woman seems to be on the rise again, with new evidence on the risks and treatment of osteoporosis and the protective effect of progestin on the endometrium becoming clearer. The risks of estrogen treatment must remain a prime concern of the practitioner, and hazards may be minimized through careful patient selection, education, examination, treatment, and follow-up. The resurgence of interest in the plight of the menopausal woman has stimulated an increasing number of competent investigators to attempt to solve the mysteries that until recently have been evaluated and treated by anecdote and homeopathic ministrations.