A comparison of the efficacy and safety of buserelin vs danazol in the treatment of endometriosis. Protocol 310 Study Group.
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Biomedical subjects
Publications and source records attributed to R B Greenblatt.
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Nonprofessional library support staff traditionally hold what are considered to be low-paying, nonchallenging positions. These negative factors make retaining creative and productive employees difficult. This article outlines the approach taken at the Medical College of Georgia's Robert B. Greenblatt, M.D. Library to devise a structure of library staff positions that becomes progressively more demanding. A new nine-level Library Staff Classification Plan resulted. This plan also enables and encourages employees to acquire more skills and to accept more responsibility in order to qualify for higher-level library positions or to advance their present position to receive comparable rewards. The plan expresses the level of responsibilities expected, the employee qualifications desired, and lists representative duties across the spectrum of typical library tasks.
Breast cyst fluids from 118 women, aged 29 to 69 years, were analyzed by radioimmunoassays for beta-human chorionic gonadotropin (beta-hCG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and thyroid-stimulating hormone (TSH). Blood was drawn at the same time in many cases to compare hormonal levels in serum with those in the breast cyst fluids (BCF). The levels of beta-hCG in BCF were relatively high, with a mean (+/- standard error of the mean [SEM]) of 58.9 +/- 16.8 mIU/ml; serum levels of beta-hCG were negligible. LH and TSH also were elevated in BCF compared with serum levels, exhibiting mean values (+/- SEM) of 26.7 +/- 4.3 mIU/ml and 6.4 +/- 0.44 muIU/ml, respectively. The levels of FSH and PRL in BCF were equivalent to the levels in the serum. The presence of biologically active hCG was suggested in several BCF samples using the rat ovarian hyperemia test. Samples of BCF were assessed for the capacity to stimulate Leydig cell testosterone production in vitro in the presence or absence of an anti-hLH antiserum. Testosterone production was significantly (P less than 0.05) enhanced, even in the presence of the antiserum. These data suggest that BCF contains biologically active hCG.
The aetiology of fibrocystic disease of the human breast remains problematical. While oestrogens may cause cystic lesions and epithelial proliferation in the mammary glands of experimental animals and certain progestogens (chlormadinone acetate and medroxyprogesterone acetate) may induce severe myoepithelial hyperplasia in beagles, the classical oral contraceptives (oestrogens and progestogens) reduce the incidence of fibrocystic breast disease in women. The role of prolactin in human breast disease is far from clear despite the fact that in rodents mammary tumors fail to develop following oestrogen administration in the absence of prolactin. Because women with gross cystic disease of the breast are at four times greater risk of developing malignant breast disease, it is felt that the administration of courses of danazol, an impeded androgen derived from the progestin, 17 alpha-ethinyl testosterone, has proved effective in lessening fibrocystic disease of the breast, frequently obviating the need for breast biopsy. The study of the hormonal content of fluid aspirated from gross breast cysts should help elucidate the pathophysiology of breast disease. Breast cyst fluid is rich in androgens, particularly dehydroepiandrosterone sulfate; concentrations of polypeptide hormones like FSH, LH, TSH, PRL, and calcitonin are invariably present sometimes in less and at other times in greater amounts than that found in plasma. Of particular interest is the finding of measurable levels of beta-hCG in cyst fluid but not in the serum. The question arises whether the beta-hCG is biologically active or are the assay values merely the expression of radioimmunoassayable components? Preliminary (as yet unpublished) studies reveal excellent bioactivity as measured by testosterone production in Leydig cell cultures. Time will tell whether elevated levels of bioactive beta-hCG portend neoplastic potential.
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Menopausal symptoms are a consequence of the decline in sex hormone production, and hormone replacement therapy aims not only to relieve these symptoms but also to prevent the development of diseases of old age such as osteoporosis. The general opinion taken from a wide variety of publications is that the serum lipid concentrations change during hormone replacement therapy with estrogen, progesterone, and testosterone, or when oral contraceptives are administered. The intolerance of many women to oral contraceptives and the many side effects developed from the birth control pill lead us to suggest that pure crystalline estrogen pellets for subcutaneous implantation are an excellent method of contraception, adding beneficial influence upon lipid metabolism by increasing HDL concentration. The use of progestogens (nortestosterone or hydroxysteroid derivatives) in order to induce withdrawal periods and to avoid endometrial hyperplasia is recommended. But it is important to note that the nortestosterone derivatives (norgestrel and norethindrone acetate) differ markedly from the nonadrogenic 17-alpha hydroxyprogesterone derivative in that the former lowers HDL levels noticeably more than the latter.
The use of androgens in the treatment of gynecic disorders has had few adherents because of the belief generally held that androgen administration to the female patient is antiphysiologic and antipharmacologic. Testosterone in physiologic doses complements estrogens and is synergestic rather than contraphysiologic. Physiologic doses of testosterone may be used to advantage in the management of the menopause, sexual dysfunction, lichen planus vel atrophicus, fibrocystic disease of the breast, and sexual infantilism resulting from hypopituitarism as well as in several other disorders.
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone were measured by radioimmunoassay in blood and seminal plasma of normo-spermic and oligospermic men. These parameters were correlated with sperm cell concentration as well as sperm motility. Average motility in the oligospermic group was significantly decreased as compared with the normospermic group (P less than .001). A significant reciprocal correlation was demonstrated between blood LH concentrations and sperm cell concentrations (P less than .05) as well as sperm motility (P less than .02). In contrast, a significant positive correlation was demonstrated between seminal LH concentrations and sperm cell count and motility (P less than .001). Seminal FSH and testosterone concentrations were positively correlated with sperm output but not sperm motility (P less than .05). The increased concentrations of LH in circulation accompanying idiopathic oligospermia suggests that LH secretion may be linked to the factors regulating spermatogenesis. The significant correlation between seminal testosterone and sperm concentration demonstrated in this study offers further support to this hypothesis. The significance of the correlation between the levels of LH and FSH in seminal plasma and sperm cell concentration and sperm motility is unknown.
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As a result of the use of synthetic luteinizing-hormone-releasing hormone (LHRH) (and its analogs), significant advances in modern clinical practice are being realized. We studied the use of LHRH as a test for pituitary reserve for gonadotropin secretion in different reproductive disorders. Synthetic LHRH was used as a diagnostic test for discriminating pituitary from hypothalamic disorders. After appropriate LHRH priming of the pituitary, LHRH was used to document hypothalamic dysfunction in patients with Kallmann's syndrome who had normal gonadotropin responsiveness to LHRH. The gonadotropin responsiveness to 100 micrograms of LHRH was impaired or absent in patients with panhypopituitarism, craniopharyngiomas, hemochromatosis and acromegaly accompanied by abnormal lactation. In women with gonadal dysgenesis, the absence of gonadal steroid feedback exacerbated the pituitary responsiveness to LHRH. Women with hyperprolactinemia are also known to have a blunted gonadotropin response to endogenous and exogenous LHRH. An experimental rat model was developed in our laboratory to study the site of prolactin action on gonadotropin secretion. LHRH challenge tests during perphenazine-induced hyperprolactinemia in rats indicated that prolactin may decrease pituitary sensitivity to LHRH. Additional experiments indicated that the increased progesterone produced in these hyperprolactinemic (pseudopregnant) rats was probably responsible for the decreased pituitary responsiveness to LHRH. Further studies will be necessary to determine whether prolactin, which can alter ovarian steroidogenesis in vitro, interferes with ovulation directly in addition to affecting the hypothalamic-pituitary axis.
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Our present knowledge of the role of sex steroids in the development as well as the prevention of endometrial cancer is reviewed. Factors which increase the exposure of the uterus to unopposed estrogens, either exogenous or endogenous, are associated with increased risk of endometrial adenocarcinoma. However, there is increasing evidence that progestogens can reverse endometrial hyperplasia and protect against the development of endometrial cancer. The mechanisms to explain the antiestrogenic effects of progestogens include changes in enzyme activity and steroid receptors in endometrial tissue. Postmenopausal women treated with combined estrogen and progestogen have the lowest incidence of endometrial carcinoma. Oral contraceptives containing both estrogen and progestogen in each tablet are protective against adenocarcinoma of the endometrium, while the sequential oral contraceptive pills afforded less protection. The risks and benefits of these hormone therapies are discussed in relation to the etiology and prevention of endometrial cancer.
Human sexual behavior is extremely complex indeed. It has been described as the sum total of an individual's makeup, which includes chromosomal sex, gender identification, gonadal adequacy, rearing, environmental influences, hormonal factors, and possible hypothalamic sensitization. In recent years, much has been written about the importance of the psyche in matters of sex and about the mechanics of coitus, as well as the proper amatory prelude. The authors think the time is ripe for an assessment of how hormones modify sexual responsiveness. In particular, they hope this article will help to dispel the notion current in many circles that hormonal therapy is of little value.
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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.
Improved diagnostic procedures and use of a new steroidal agent, danazol (Danocrine), should reduce the need for surgical intervention in fibrocystic breast disease. Thermography, a non-invasive procedure that may be used with impunity, may help identify women at high risk. Mammography, which is useful in revealing malignancy in an early stage, should be done in women with tow consecutive abnormal thermograms. Biopsies should be performed, however, on suspicious, firm, irregular masses, regardless of results on thermography or mammography. Use of danazol may be advantageous not only in ameliorating pain and eliminating nodosities, but also in guiding the surgeon to the nodule that is unresponsive to treatment and therefore should be evaluated by biopsy.
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Fibrocystic disease of the breast (FCD) is an exaggeration of the normal physiologic response to cyclic estrogen and progesterone stimulation. The disorder can persist, with much less severity, in the menopausal woman. Whether FCD predisposes to mammary cancer remains moot. A new steroidal agent, danazol, can eliminate nodosities in the majority of women with FCD. Thermography may identify women who are at greater risk because of increased heat production. Mammography should be employed in women with persistently abnormal thermograms, even though no suggestive breast masses are palpable. Needle biopsy or surgical biopsy should be undertaken whenever a firm indurated mass is palpated, regardless of negative findings with a thermogram or mammogram. In a series of 1548 women treated for 10,715 women-years, the incidence of breast cancer after prolonged estrogen therapy was not increased. Although estrogens and prolactin have been incriminated in the etiology of mammary cancer, no hard facts exist to confirm such allegations.