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Biomedical subjects

R D Gambrell

Publications and source records attributed to R D Gambrell.

At least 55 records · Page 3Linked to original sources

Decreased incidence of breast cancer in postmenopausal estrogen-progestogen users.

In a prospective study at Wilford Hall USAF Medical Center from 1975 to 1981, 5563 postmenopausal women were followed for a total of 37,236 patient-years of observation. During these seven years, 53 patients were found to have breast cancer, for an incidence of 142.3:100,000 women per year. The mean age (+/- SD) of the patients with cancer was 56.9 +/- 8.24 years, and the mean age of the entire patient population was 56.8 +/- 6.75 years. The expected incidence of breast cancer in this age group, according to the Third National Cancer Survey (1975), is 188.3:100,000 women, and for ages 55 to 59, according to the National Cancer Institute Surveillance, Epidemiology, and End-Result Reporting (NCI SEER) data (1980), is 229.2:100,000. The lowest incidence of breast cancer (67.3:100,000) was observed in the estrogen-progestogen users and was significantly lower than that of the untreated group (342.3:100,000), with P less than or equal to .01. The incidence of the estrogen-progestogen users was also significantly lower than that expected from the NCI SEER data, with a relative risk of 0.3 (95% confidence interval, 0.1 to 0.8). The incidence of mammary malignancy in the estrogen users (141.0:100,000) was significantly lower than in the untreated group (342.3:100,000), with P less than or equal to .01. Although the incidence in the estrogen users was not significantly lower than that expected according to the NCI SEER data (relative risk = 0.7, 0.5 to 1.1), there was a trend in that direction. These data indicate that estrogen therapy for postmenopausal women does not increase the risk of breast cancer and may afford some protection. Added progestogen to postmenopausal estrogen therapy significantly decreases the risk for this malignancy.

Adult↗

The protective role of progesterone in the prevention of endometrial cancer.

An association between endometrial hyperplasia and corpus cancer has long been suspected. Genetically predisposed women are at greater risk of developing endometrial cancer if subjected to long uninterrupted period of estrogen stimulation. Endometrial cancer need not be inevitable if 14 day courses of an oral progestogen are continued for as long as is necessary; in some women, however, the lesions will progress and, therefore, should be carefully followed with repeated endometrial biopsies. Epidemiological evidence suggests a true link between unopposed estrogens and early, less invasive endometrial cancer, and progestogens appear capable of protecting against the development of cancer and hyperplasia, although complete protection has not yet been achieved. The protective action of progestogens is supported by the fact the none developed endometrial cancer in a series of 490 women of reproductive age who received continuous estrogens by way of pellet implants of 17 beta estradiol for conception control for 1--10 years. Evidence for the protective action of progestogens in estrogen-treated menopausal women was less solid than in non-menopausal women but was nonetheless considerable. Our study of 1058 women, 45 years of age and older, receiving continuous estrogens by way of 17 beta estradiol pellets over a period varying from 1 to 21 years, revealed that the incidence of cancer was not greater and was possibly less than that expected in an untreated population of menopausal women.

Adolescent↗

Clinical use of progestins in the menopausal patient: dosage and duration.

Although estrogens are the principal hormone needed by postmenopausal women, there are many benefits of progestins. There is some increased risk of endometrial cancer from estrogen-replacement therapy; however, added progestin decreases this risk to less than that observed in untreated postmenopausal women. Climacteric women at the greatest risk of endometrial cancer can be identified by the progestin challenge test. There may also be some protection from breast cancer in progestin-treated postmenopausal women. Progestins are effective in managing the increased breast tenderness and aggravation of fibrocystic breast disease that may occur in some estrogen-treated postmenopausal women. Both estrogens and progestins are effective in retarding the progression of osteoporosis, but estrogen-progestin combination therapy may promote new bone formation. Long-acting injectable progestins are effective in relieving vasomotor symptoms. Finally, progestins also reduce the incidence of postmenopausal bleeding and the necessity of diagnostic curettage. The progestin should be continued for ten days each month as long as the patient experiences withdrawal bleeding. When withdrawal bleeding ceases, the progestin may be discontinued. However, the progestin challenge test should be repeated annually to ensure that the endometrium is not being stimulated by either exogenous therapy or increased endogenous estrogens.

Adenocarcinoma↗

Role of hormones in the etiology and prevention of endometrial and breast cancer.

Although there is a slightly increased risk of endometrial cancer from estrogen therapy for menopausal women, progestogens given along with the estrogen significantly decrease the incidence of this malignancy to a rate lower than that of untreated women. Postmenopausal women predisposed to adenocarcinoma of the endometrium because of increased endogenous estrogens can be identified with the progestogen challenge test and treated with cyclic progestogens for 10 days each month to prevent endometrial cancer. Oral contraceptives containing both estrogens and progestogens in each tablet are protective against developing adenocarcinoma of the endometrium, whereas the sequential birth control pills provided less protection. The incidence of breast cancer is significantly lower in both estrogen and estrogen-progestogen users than in postmenopausal women never using these hormones. In those women found to have breast cancer while using these hormones, the prognosis is better than that found in women never exposed to exogenous estrogens, most likely due to an earlier detection. No clear-cut pattern of either abnormal hormone production or milieu has been found in women with carcinoma of the breast. Oral contraceptives reduce the risk of benign breast disease and afford some protection from the subsequent development of breast cancer. The mortality rate from breast cancer developing in oral contraceptive users is significantly lower than that of the non-users.

Breast Neoplasms↗

Changes in thyroid function tests during danazol therapy.

Danazol is a synthetic steroid with antigonadotropic properties useful in treating endometriosis, especially in young infertile women. Prior to its availability for clinical use in September 1976, thyroid function studies other than thyroid-stimulating hormone (TSH), which was normal, had not been reported. Soon after danazol began to be used in the infertility clinic to treat documented endometriosis, it was observed that changes occurred in thyroid function studies. While no patients manifested clinical evidence of hypothyroidism, all 8 patients receiving 800 mg of danazol daily for 1 to 5 months had laboratory evidence of decreased thyroid function. The triiodothyronine (T3) uptake was elevated and the total serum thyroxine (T4) was decreased. The finding that TSH and the free thyroid index (FTI) were normal confirmed that these patients were euthyroid during danazol therapy. The abnormality of thyroid function tests is believed to reflect an androgen-like reduction in thyroxine-binding protein rather than a true decrease in thyroid function or interference with the pituitary-thyroid axis.

Danazol↗

Estrogen therapy and breast cancer in postmenopausal women.

During the 6-year period 1972-77, 123 postmenopausal women with breast cancer either had the disease diagnosed at Wilford Hall USAF Medical Center or were referred there for therapy. Their ages ranged from 33 to 90 (mean, 56.6 years). Of these women 64.2 percent had never taken hormones, 25.2 percent were estrogen users, 4.9 percent were estrogen-progestogen users, 4.9 percent had a history of hormone usage, and 1 patient was using estrogen vaginal cream. In a subgroup of 27 clinic patients (1975-77 period) during 14,548 patient-years of observation, breast cancer was diagnosed for an overall incidence of 185.6:100,000 women per year. Among the 27 patients, the annual incidence of breast cancer was highest in the untreated group at 410.5:100,000 women. In comparison, the incidence in the estrogen users was 137.7:100,000 women-a significant difference (p less than 0.01). The incidence in estrogen-progestogen users was 155.6:100,000 compared with the incidence in the untreated patients; this difference was also statistically significant (p less than 0.05). There was no significant difference in the incidence of breast cancer between the estrogen users (137.7:100,000) and the estrogen-progestogen users (155.6:100,000). These data indicate that estrogen therapy decreases the risk of breast cancer and that, unlike the situation with adenocarcinoma of the endometrium, progestogens do not offer additional protection from breast carcinoma.

Adult↗

Use of the progestogen challenge test to reduce the risk of endometrial cancer.

In contrast to several retrospective studies reporting an increased risk of endometrial cancer during the mid-1970s, especially in estrogens.gen-treated postmenopausal women, the number of cancers at Wilford Hall USAF Medical Center has steadily declined despite continued estrogen use. In a 4-year study from 1975 to 1978, there were 17 adenocarcinomas of the endometrium during 10,872 patient-years of observation, for an overall annual incidence of 156.4:100,000 women. The highest incidence of endometrial cancer (359.1:100,000) was found in those women using estrogens alone. The lowest incidence of cancer was observed in the estrogen-progestogen users (56.4:100,000) and was significantly lower (P less than .01) than that found in the estrogen users. The incidence of corpus malignancy in the estrogen-progestogen users was also significantly lower (P less than .05) than that observed in the untreated women (248.3:1000,000). The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma of the endometrium. It is concluded that the use of this test will reduce the risk of endometrial cancer in both estrogen-treated postmenopausal women and women with increased endogenous estrogens.

Adenocarcinoma↗

Amenorrhea secondary to voluntary weight loss.

Obese patients who voluntarily reduce to a normal weight may develop secondary amenorrhea. Six young women who dieted to lose from 13 to 50 pounds, including four from an obese weight, were evaluated because of absent cervical mucus ferning, hypoestrogenic vaginal smears, and failure to have withdrawal menses from a progestogen. Serum FSH values were normal in all, while four had normal serum LH and two had low serum LH levels. T4 and/or T3 uptake was normal in all. The pituitary-adrenal axis was apparently intact since baseline urinary steroids were normal as was the response to both ACTH and metyrapone. Fasting serum growth hormone was markedly elevated in two and slightly elevated in three, with the other patinet demonstrating an unusually high response to glucagon/propranolol in the 30 minute specimen. These endocrine findings are similar to those observed in patients with anorexia nervosa, but the weight loss is entirely voluntary and there was no associated psychiatric abnormality.

Adolescent↗

The role of hormones in the etiology of breast and endometrial cancer.

Despite many years of extensive investigation, there has been neither a clear-cut pattern of hormonal production nor milieu found in women with breast cancer. Estrogen replacement therapy for menopause does not significantly increase the risk of breast cancer and one study indicated that estrogen users have a lower incidence of breast cancer than that observed in untreated women. Some studies have shown that the mortality rate from breast cancer is lower in estrogen-treated postmenopausal women. Only one investigator has found any significantly increased risk of breast cancer in oral contraceptive users. In that report, increased duration of birth control pill use decreased the risk of breast carcinoma. Several studies were unable to find an increased risk of breast cancer from oral contraceptives while one investigation observed a lower incidence in birth control pill users than that expected. The mortality from carcinoma of the breast in oral contraceptive users was lower than in non-users, most likely due to earlier detection. Although some retrospective studies have indicated that estrogen use increases the risk of endometrial cancer, a prospective investigation found only an insignificant increase. Progestogens afford some protection from cancer in estrogen-treated postmenopausal women. The incidence of endometrial adenocarcinoma is lower than that observed in untreated postmenopausal women. Combination oral contraceptives are protective against developing adenocarcinoma of the endometrium but sequential birth control pills may afford less protection.

Adult↗

Antepartum pituitary infarction.

Antepartum pituitary infarction occurs only in insulin-dependent diabetic patients. It is manifested by severe headache, followed by decreasing insulin requirements. Delivery is frequently premature, with high fetal wastage and increased maternal mortality. During the puerperium, the first manifestation of pituitary deficiency, other than a lower insulin requirement than would be expected, is failure to lactate. Subsequent evaluation of pituitary function reveals variable deficiencies with loss of growth hormone and gonadotropins being most frequent. This case is the eighth report of this entity, and it represents the first patient to survive a pituitary infarction prior to the third trimester of pregnancy. Recognition of this syndrome is critical in order to ensure that the mother's health and the viability of the offspring be preserved.

17-Hydroxycorticosteroids↗

Complete and partial vaginal agenesis.

The proper diagnosis and treatment of a patient with vaginal agenesis demands a thorough knowledge of the relevant embryology, anatomy and physiology as well as sensitivity to the potentially emotionally devastating effects of the condition. Ten patients with vaginal agenesis were evaluated and treated at Wilford Hall USAF Medical Center over a three-year period. The patients fell into three groups, those with: (1) Müllerian atresia, complete or partial; (2) maldevelopment of the lower one-third of the vagina; and (3) testicular ferminization. Other congenital anomalies existed in many of these patients. Most of the patients were treated with the Frank method of vaginal development with good results. Some underwent surgical correction.

Abnormalities, Multiple↗