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Biomedical subjects

D Shoupe

Publications and source records attributed to D Shoupe.

At least 19 recordsLinked to original sources
PubMed1996

Phase I prehysterectomy studies of the transcervical administration of quinacrine pellets.

To determine the safety of transcervical administration of quinacrine pellets as a method of voluntary female sterilization, three noncomparative Phase I clinical trials of the administration of 250 mg quinacrine were carried out in 21 women who were scheduled to undergo hysterectomy 24 h or one month later. Detailed results are presented for one of the trials using 10-min pellets. Six of 10 women had minor transitory complaints during the postinsertion 24-h follow-up period. Five women reported pelvic/abdominal cramping, one experienced headache, and one experienced dizziness. Blood chemistry values were not adversely influenced by the quinacrine. The average plasma level of quinacrine peaked at 3 h, 36.1 ng/ml, slightly lower than the value observed 4 h after oral administration of 200 mg in a previous study. An average of 27% of the administered dose was recovered in tampons. Quinacrine was detected in the plasma of two women at the four/six-week visit. Selected results are presented from two other trials that were halted because of slow recruitment. The transcervical administration of 250 mg of 10-min quinacrine pellets was well tolerated. However, based on recent mutagenicity testing and meetings with regulatory officials, it appears unlikely that the use of quinacrine for nonsurgical sterilization could be approved in the United States or Europe.

Abdominal Pain↗
PubMed1996

Contraception in the 1990s.

Contraceptive technology has recently provided the market place with new barrier methods, new progestin oral contraceptives, an injectable contraceptive, the female condom, new male condoms, and the contraceptive implant. During the last decade, epidemiologists have clearly defined the non-contraceptive benefits of current contraceptive methods that include decreased infections, protection from various cancers, protection from many gynecologic problems that lead to surgery, as well as symptomatic relief from many gynecologic conditions. In conjunction with medical specialists, contraceptive researchers have established the increased safety and benefits of various contraceptive choices in women with medical conditions that, until recently, were contra-indications for their use. That these advances have occurred despite multiple legal and scientific assaults gives hope that the field will continue to grow.

Contraception↗
PubMed1994

Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk.

BACKGROUND: It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia. PURPOSE: Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group. METHODS: Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists. RESULTS: Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance. CONCLUSION: The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.

Adult↗
PubMed1994

A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol.

A core design contraceptive vaginal ring (CVR) releasing 650 mcg of norethindrone acetate (NA) and 10, 20, 30 or 65 mcg of ethinyl estradiol (EE) daily was developed and tested in 99 women. The CVR inhibited ovulation well with 30 or 65 mcg EE. Vaginal bleeding was better controlled than in 23 control women using NA/EE oral contraceptives. Side effects were comparable to controls for the 20 and 30 mcg EE CVR. The 65 mcg EE CVR resulted in an unacceptably high level of nausea. The 20 and 30 mcg EE CVR caused an increase in serum HDL cholesterol and triglycerides. Total cholesterol was unchanged. Angiotensinogen and sex hormone binding globulin-binding capacity were increased in a subgroup of the 20 and 30 mcg EE CVR subjects, similar to that of 20 controls using EE/gestodene oral contraceptives. This new CVR offers an excellent contraceptive alternative with the best performance provided by the 30 mcg EE dose.

Administration, Intravaginal↗
PubMed1994

New progestins--clinical experiences: gestodene.

Gestodene, one of three new gonane progestins, is the most potent on a per weight basis in regard to progestational effects and has little or no estrogenic effect. In in vivo animal studies, gestodene also has less androgenic activity compared with progestins found in older combination oral contraceptive formulations. It binds to mineralocorticoid receptors and consequently is a competitive aldosterone inhibitor, leading to speculation that it may be beneficial in hypertensive patients. Numerous large clinical trials have shown that the combination of gestodene and ethinyl estradiol is as effective in preventing pregnancies as other oral contraceptives presently on the market. Irregular bleeding and spotting rates appear to be at least as good as older formulations. In general, studies show that the incidence of side effects associated with the progestin and estrogen components tends to be low, with very little impact on lipid and carbohydrate metabolism. Gestodene-containing oral contraceptives have been associated with small increases in clotting factors, generally because of the estrogen component, with compensatory changes in the fibrinolytic system. Although gestodene-containing oral contraceptives have been used in Europe since 1987, they have not been available in the United States except for use in clinical trials. At present, a triphasic formulation containing 50 to 100 micrograms of gestodene plus 30 to 40 micrograms of ethinyl estradiol is awaiting approval by the Food and Drug Administration.

Blood Coagulation↗
PubMed1994

Depot leuprolide acetate with estrogen and progestin add-back for long-term treatment of premenstrual syndrome.

OBJECTIVE: To test the effectiveness and safety of long-term depot leuprolide acetate (GnRH-a) plus estrogen and progestin add-back therapy in the treatment of moderate and severe premenstrual syndrome (PMS). DESIGN: A prospective trial with each patient serving as her own control. SETTING: University teaching hospital. PARTICIPANTS: Ten women with regular menstrual cycles complaining of moderate to severe PMS. Premenstrual syndrome was diagnosed when symptoms increased > or = 25% during the luteal phase. TREATMENT: Four-week cycles of IM injections of placebo or GnRH-a with all patients receiving saline (placebo), the first cycle followed by 12 cycles of GnRH-a, 7.5 mg. Conjugated equine estrogen (0.625 mg/d) was started Monday through Saturday within the first cycle and increased as needed. Medroxyprogesterone acetate (MPA), 10 mg/d, was taken orally for 10 days after 4, 8, and 12 cycles of GnRH-a therapy. MAIN OUTCOME MEASURES: Changes in three symptom categories (water retention, pain, and psychological function), serum levels of total cholesterol and HDL, HDL-2, and LDL cholesterol, E2, and estrone. Endometrial biopsy was obtained 1 day after the end of the 12th GnRH-a cycle, and bone density was assessed using quantitative computer tomography at the end of the 12th GnRH-a cycle. RESULTS: During treatment, there was a significant decrease compared with baseline and placebo in all three symptom categories. There were no significant changes in lipids. Endometrial biopsies revealed progestational changes with no evidence of hyperplasia. Quantitative computer tomography bone density dropped 3.7 on average compared with baseline after 12 months of treatment, but this was not statistically significant. CONCLUSION: Gonadotropin-releasing hormone agonist therapy with hormonal add-back therapy is effective in treating PMS symptoms with progressive improvement over a 12-month period. This therapy prevents changes in lipids and adequately protects the endometrium with the addition of MPA every 4th cycle. Quantitative computer tomography bone density dropped at 12 months; further examination of bone changes is necessary.

Adult↗
PubMed1994

Multicenter randomized comparative trial of two low-dose triphasic combined oral contraceptives containing desogestrel or norethindrone.

OBJECTIVE: To compare a new triphasic oral contraceptive (OC) containing desogestrel and ethinyl estradiol (DSG/EE) with triphasic norethindrone/ethinyl estradiol (NE/EE) regarding effects on clinical efficacy, cycle control, and safety indices. METHODS: In an open-label, comparative multicenter study, 407 subjects were randomized to a triphasic preparation containing DSG/EE and 405 subjects to a triphasic preparation containing NE/EE. The women were observed during six cycles of OC use. RESULTS: The contraceptive efficacy of the triphasic DSG/EE OC was at least comparable to that of triphasic NE/EE. No pregnancies were reported with DSG/EE, whereas there were two pregnancies with NE/EE, both user failures. Cycle control with triphasic DSG/EE was statistically superior to that with triphasic NE/EE. Acceptability was excellent with both preparations as measured by the low discontinuation rates (particularly for adverse menstrual experiences). No thromboembolic or other serious drug-related adverse experiences were reported. The incidence of other drug-related adverse experiences was generally low and decreased with time in both groups. No adverse effects were seen in terms of blood pressure, body weight, laboratory indices, cervical cytology, and breast nodularity. CONCLUSION: Triphasic DSG/EE is an effective and safe OC with excellent acceptability and cycle control superior to that of triphasic NE/EE.

Adolescent↗
PubMed1993

Effects of desogestrel on carbohydrate metabolism.

Associated with progesterone and the synthetic progestins used in oral contraceptives is a dose-dependent impairment of carbohydrate metabolism. It is well known that in the general population hyperinsulinemia and alterations in glucose metabolism are significant risk factors for the development of cardiovascular disease. Studies that use curve analysis of glucose tolerance tests have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance in women using oral contraceptives. Desogestrel, a new progestin, has been demonstrated to have generally less pronounced effects on these parameters of carbohydrate metabolism.

Animals↗
PubMed1993

Pilot trial of a gonadotropin hormone agonist with replacement hormones as a prototype contraceptive to prevent breast cancer.

Combination oral contraceptive (COC) users have reduced risks of ovarian and endometrial cancer, but COCs have not reduced breast cancer risk. We have previously argued that a hormonal contraceptive with substantially lower doses of sex-steroids should reduce breast cancer risk by decreasing the breast epithelial cell proliferation below usual premenopausal levels. We report here the preliminary results of a pilot trial with such a prototype contraceptive consisting of an agonist of gonadotropin releasing hormone (GnRHA) administered with low doses of an oral estrogen (0.625 mg of conjugated estrogen, CE, for 6 days every week) and intermittent oral progestogen (10 mg of medroxyprogesterone acetate, MPA, for 13 days every 4 months). Eighteen subjects at five-fold or greater increased breast cancer risk were entered and randomized -12 to the contraceptive arm and 6 to a control arm. The principal endpoints included tolerance of the regimen, vaginal bleeding patterns, and the regimen's effect on the endometrium, bone metabolism, and lipids. A symptom questionnaire was used to assess tolerance; the contraceptive subjects had fewer symptoms following initiation of the regimen. This results from the elimination of symptoms associated with the luteal phase of the menstrual cycle, commonly referred to collectively as premenstrual syndrome, PMS. The few occurrences of hot flushes or vaginal dryness that did occur were eliminated by small increases in estrogen dose (0.9 mg CE). Scheduled vaginal bleeding occurred associated with most periods of progestogen administration. Unscheduled bleeding or spotting was infrequent and decreased with time on the regimen. A beneficial rise in high-density lipoprotein cholesterol was evident in the contraceptive subjects. Despite the use of an estrogen dose which is known to prevent loss of bone mineral density in normal postmenopausal women, an annualized loss of 1.9% was seen in contraceptive subjects. It is hypothesized that this is secondary to inhibition of ovarian androgen production by the GnRHA, which may additionally account for changes in libido occasionally reported with GnRHA. The study continues with the addition of a small dose of androgen to replace that lost by the action of the GnRHA.

Adult↗
PubMed1993

Luteal phase defects.

Luteal phase defects are defined as disorders resulting from abnormal corpus luteum function associated with insufficient progesterone production. The incidence is difficult to estimate accurately, but the disorder may affect 3-4% of infertile couples. Candidates for screening are those with unexplained infertility or recurrent abortion. Blood samples should be obtained seven to nine days after ovulation as determined by the thermogenic shift on basal body temperature monitoring or by a urinary luteinizing hormone surge. A midluteal phase serum progesterone level < 10 ng/mL is suggestive of the diagnosis. Endometrial biopsies are indicated in those couples with unexplained infertility and recurrent abortion, particularly if progesterone levels are > 10 ng/mL. While there have been few comparative studies, the four treatments available are clomiphene citrate, progesterone vaginal suppositories, human menopausal gonadotropins and bromocriptine. Because of its simplicity of use, clomiphene citrate is the recommended first-line treatment.

Female↗
PubMed1991

GnRH agonists as contraceptive agents: predicted significantly reduced risk of breast cancer.

Gonadotrophin-releasing hormone agonists (GnRHAs) were investigated as contraceptive agents from the late 1970's to the mid-1980's. They were abandoned as they appeared to offer no advantage over conventional combination-type oral contraceptives (COCs). This conclusion appears to be incorrect. We propose here a contraceptive regimen of a depot formulation of a GnRHA plus add-back estrogen and intermittent progestogen. The dose of add-back sex-steroids is substantially less than that in COCs; this reduction in sex-steroids should lead to a major reduction in lifetime breast cancer occurrence.

Bone and Bones↗
PubMed1991

The significance of bleeding patterns in Norplant implant users.

The purpose of this study was to examine the bleeding patterns of 234 Norplant users during 5 years of use and to identify the bleeding patterns of users who conceived. During the first year of use, 26.6% of users had regular bleeding cycles, 66.3% had irregular cycles, and 7.1% were amenorrheic. By the fifth year of use, 62.5% of users had regular cycles, 37.5% had irregular cycles, and none had amenorrhea. Of the ten users who became pregnant, eight had regular menstrual cycles in the 6 months before the diagnosis of pregnancy, one had an irregular pattern, and one did not keep a bleeding record. None had amenorrhea. The 5-years cumulative pregnancy rate for patients with regular cycles was 17.4%; this was significantly higher (P less than .05) than the 5-year cumulative rates of 4.4% in users with irregular cycles and 0% in users with amenorrhea. This study indicates that during the first year of Norplant use, only 26.6% of users have regular cycles, but after the first year, 50-60% of users develop regular cycles. The bleeding patterns of women using Norplant improve after the first year of use, and those with regular cycles are at greatest risk for method failure.

Contraceptive Agents, Female↗
PubMed1991

Characteristics of ovarian follicular development in Norplant users.

Daily transvaginal ultrasound (US) scanning of the ovaries to assess follicular development and daily blood sampling were performed on 19 Norplant (Leiras, Turku, Finland) subdermal contraceptive implant users who had regular menstrual cycles and on 10 normally cycling women. Three groups were identified in the implant users based on US finding. Six (31.6%) of the implant users had US findings that were consistent with a normal ovulatory pattern. However, their mean peak luteinizing hormone levels and peak midluteal phase progesterone (P) levels were significantly lower than control values. Eleven (57.9%) users had persistent follicles, and 2 users (10.5%) had no follicular development. These data suggest that after 2 to 4 years of use, about one third of Norplant users with regular bleeding patterns may ovulate but most have deficient luteal P levels. In this small study, the presence of persistent follicular enlargement in implant users was common.

Contraceptive Agents, Female↗
PubMed1991

Postmenopausal hormone replacement with a combination estrogen-progestin regimen for five days per week.

A group of 15 postmenopausal women who had not recently received estrogen replacement were enrolled in a study during which they received 0.625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate daily from Monday through Friday of each week for six months. No treatment was given on the weekend. Endometrial biopsy specimens at the end of therapy revealed minimal growth of glands and stroma and a low mean mitosis count. Of the 12 women who completed the trial, 5 were completely amenorrheic, and only 4 of the 15 bled beyond the second month of treatment. Of those four, two spotted for only a few days. In the 12 women who completed the trial there was a significant increase in high density lipoprotein cholesterol and a nonsignificant lowering of low density lipoprotein cholesterol. The results of this study indicate that comparative trials between this regimen and one in which the two drugs are given daily for seven days a week are warranted.

Adult↗
PubMed1990

Effect of low-dose oral contraceptives on carbohydrate and lipid metabolism in women with recent gestational diabetes: results of a controlled, randomized, prospective study.

Women with recent gestational diabetes mellitus were randomly assigned to one of two low-dose oral contraceptives to evaluate the effect of low-dose oral contraceptives on carbohydrate and lipid metabolism. A cohort of similar women requesting a non-oral-contraceptive method served as controls. The two oral contraceptives studied were ethinyl estradiol (0.035 mg)-norethindrone (0.40 mg) and ethinyl estradiol (0.030 to 0.040 mg)-levonorgestrel (0.050 to 0.125 mg). A 75 gm, 2-hour oral glucose tolerance test and a fasting lipid profile (total cholesterol, triglyceride, high- and low-density lipoprotein cholesterols) were performed at entry, after 3 months, and after 6 to 13 months of treatment. The prevalence of diabetes at 6 to 13 months (27/156 patients) was not significantly different between groups (non-oral-contraceptive group, 17%; ethinyl estradiol-norethindrone, 15%; ethinyl estradiol-levonorgestrel, 20%). When examined by prior gestational diabetes mellitus class, diabetes mellitus was present in 7% of prior class A1 and 29% of women with prior class A2 disease (p less than 0.001). Mean cholesterol and low-density lipoprotein cholesterol levels were significantly improved in all three groups at 3 months and at 6 to 13 months, whereas triglycerides remained unchanged. There were no differences in cholesterol, low-density lipoprotein cholesterol, or triglycerides levels between the groups. After 6 to 13 months, there was a significant increase in high-density lipoprotein cholesterol in the ethinyl estradiol-norethindrone group compared with the ethinyl estradiol-levonorgestrel and non-oral-contraceptive groups.

Adult↗