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.
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Forty-nine women diagnosed as having pelvic endometriosis were treated with 800 mg of danazol/day for a mean duration of 6 months. The average length of the follow-up period was 78 months. Side effects were minimal, and regular ovulatory menses returned within 25 to 90 days (average 42 days). Forty-two (85.7% of these women had associated infertility. Recurrence of symptoms was reported in 33% but in no patient were the symptoms worse than before entering the study. Of 30 patients desirous of pregnancy, 20 were potentially fertile; of these, 10 conceived within 6 months of discontinuing therapy, for a conception rate of 50%. Nine of the remaining ten patients required additional therapeutic procedures (surgery and/or danazol), and four of these conceived within 12 months. These results compare favorably with those of other investigations, since most of our patients were referred to us after being subjected to a variety of regimens, both hormonal and surgical.
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The case of a patient with premature ovarian failure and a history of polycystic ovarian disease was described. Dynamic gonadal and pituitary tests were done. Ovarian, adrenal, and peripheral veins were catheterized to determine the steroid secretion under HCG stimulation. In vitro studies of the capacity of ovarian steroidogenesis confirmed the refractory nature of the gonad. Lack of gonadal response, both in vivo and in vitro, to stimulation suggests a possible alteration in ovarian sensitivity to gonadotropins as a possible cause of premature menopause.
Serum estrone, estradiol, progesterone, FSH, and LH levels were studied after the implantation of estradiol pellets in female volunteers in the reproductive age group. The estradiol pellets were implanted at six-month intervals. The first implant consisted of four pellets (25 mg each). Subsequent implants consisted of a reduction by one pellet as compared to the previous implant. The mean serum estradiol levels during the six-month period of implantation or at the end of six-month intervals were in the premenopausal range and did not differ significantly during the study. The serum estrone levels showed a tendency to increase with time even though the number of pellets implanted was decreasing, apparently a result of incomplete absorption of the implanted estradiol during the six-month period. The results of serum progesterone determinations and basal body temperature records indicate that the suppression of ovulation takes place most consistently during the second and subsequent months after estradiol pellet implantation.
The gonadal steroids--estrogens and androgens--appear to have a mood-elevating, psychotonic effect. The improved sense of well-being and increased vigor probably is engendered by restoration of somatic efficiency and psychic equilibrium. 1. The male climacteric, as observed in a limited number of men, is associated with a low level of serum testosterone. The levels of follicle-stimulating hormone and luteinizing hormone are not elevated because estrogen concentration continues unaltered well into old age. Androgen replacement therapy often lessens fatigue, depression and headaches, and headaches, and improves libidinous drives. 2. In the aging female, many climatric symptoms other than those due to vasomotor instability were heretofore considered merely coincidental. Recent studies suggest that the metabolism of cerebral hormones is markedly influenced by endogenous and exogenous gonadal steroids. Thus, postmenopausal depression, headaches, and nervousness may be hormone-dependent symptoms. 3. The incidence of endometrial cancer is no greater and is probably less in estrogen-treated women than in women not treated with estrogen, if regular cyclic courses of an oral progestogen are added to the regimen.
Relationships between the hypothalamus and the pituitary in the aging woman are discussed under the following subheadings: synthesis and release of follicle-stimulating and luteinizing hormones, estrogen receptors, other releasing factors, neurotransmitters, and the mechanisms of hot flushes and migrainoid headaches. The hypothalamus is the main regulator of pituitary function. In the female the hypothalamic-pituitary axis appears to remain functionally intact well into old age.
Cushing's syndrome is characterized by protein wasting secondary to hypergluconeogenesis, which produces thin skin, poor muscle tone, osteoporosis and capillary fragility. These features distinguish patients with true Cushing's syndrome from those who have some of the clinical findings often associated with the syndrome, such as obesity, hypertension, striae and hirsutism. The dexamethasone suppression test helps identify patients with pseudo-Cushing's syndrome.
Estriol was administered for a six-month period as estrogen replacement therapy to 52 symptomatic postmenopausal women. Assays of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone, and estradiol were performed before and during therapy. During this period of administration, vaginal cytology, cervical mucus, and endometrial studies were performed. Clinical effectiveness was directly related to dosage (2 to 8 mg/day). Estriol (8 mg/day) failed to induce endometrial proliferation and proved a poor suppressor of FSH and LH. This agent's capacity to relieve vasomotor instability and improve vaginal maturation without notable side effects is sufficient reason to include this drug in the management of the postmenopausal syndrome.
Organic, physiologic, and psychologic causes of dysmenorrhea are presented. Signs and symptoms include pelvic fullness, nausea, vomiting, diarrhea, urinary frequency, nervousness, and headaches. Primary dysmenorrhea has been treated with analgesics, diuretics, and antispasmodics. Androgen therapy was also found to be effective, but it cannot be used for women who have acne or hirsutism. Surgery is rarely indicated for primary dysmenorrhea.
Postmenopausal women should not be denied estrogen therapy because of the controversy about the alleged causal relationship of estrogens to endometrial cancer. A prestigious team of biostatisticians reviewed three publications that claimed this relationship and concluded that no such association could be confirmed. Although the incidence of endometrial cancer has doubled in the past 25 years, there is no valid basis for the assumption that the widespread use of estrogens is the cause. The incidence also has increased in Norway and Czechoslovakia where estrogens are rarely used. Moreover, the histologic pattern of endometrial dysplasias is such that many pathologists will make a diagnosis of endometrial cancer as a safeguard for the patient. Thus the statistics for the incidence of endometrial cancer may be inflated. As a test, the administration of 200 mg of an oral progestogen over 5-10 days will convert a histologic pattern of pseudomalignancy, but not of adenocarcinoma, into one of secretory endometrium. Unopposed endogenous or exogenous estrogens may induce hyperplasia, atypical adenomatous hyperplasia or adenocarcinoma in women who are genetically predisposed. To minimize such a possibility, it is advisable to give a 5-7 day course of an oral progestogen so that the endometrium will be shed as monthly intevals. The benefits of hormone replacement therapy for the postmenopausal woman far outweigh the putative risk of endometrial cancer.
The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.
Eight of 115 patients with empty sella had concurrent galactorrhea. All 8 patients had abnormal sellae, and the diagnosis of empty sella was made by polytome pneumoencephalography. There were no obvious endocrine dysfunctions, but 2 patients had elevated prolactin levels. One mechanism for production of galactorrhea may involve compression of the hypothalamus and/or pituitary stalk; this was suggested by most of our observations. There may be a coincidental association of empty sella with galactorrhea, and this association is probably more common than previously noted. Evaluation of patients with galactorrhea and abnormal sellae by polytome pneumoencephalography is emphasized.