Biomedical subjects

D F Archer

Publications and source records attributed to D F Archer.

At least 55 records · Page 3Linked to original sources

PubMed1996

Management of irregular uterine bleeding and spotting associated with Norplant.

Norplant, a systemic contraceptive, has been used extensively throughout the world. A major problem for consumers utilizing Norplant has been irregular, unpredictable uterine bleeding or spotting. This study seeks to determine whether or not an appropriate treatment could be found that will reduce the incidence of spotting and bleeding. Both a pilot study and an interim report of a multi-center trial utilizing ethinyl estradiol 20 micrograms for 10 days, versus Ibuprofen 800 mg three times a day for 5 days, versus placebo is reported. Based on the interim analysis of the multi-center trial, there is a reduction in the mean number of spotting days with one of the three treatments compared to the other two treatments (p = 0.044). There was no difference in the number of bleeding days between treatment regimen. It appears from a review of the literature that both oestrogen, progesterone, and non-steriodal anti-inflammatory agents may reduce the number of bleeding days or inhibit acutely the bleeding in women utilizing Norplant. The completion of this randomized multi-center trial will hopefully give us further insight into an effective treatment for controlling the irregular bleeding and/or spotting that occurs in Norplant users.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1996

Mifepristone: a potential contraceptive.

Use of standard estrogen-progestin contraception remains problematic in several subgroups of patients (e.g., those in whom exogenous estrogens are contraindicated, such as survivors of hormone-dependent cancer, or patients with endometriosis or uterine fibroids). In addition, the postcoital contraception, even if already available, remains at least underused. Additionally, continuous intake of contraceptive steroids is under increasing scrutiny. Would antiprogestins, and specifically the applications of mifepristone such as the ones reviewed in this article offer significant improvements at such problematic occasions? The most attractive novel contraceptive application of mifepristone is that of emergency postcoital contraception after unprotected intercourse. In addition, various options in the endometrial category, specifically those requiring drug administration only during a limited time, might be used in the future. Mifepristone might offer contraceptive and therapeutic relief to patients suffering from endometriosis or uterine fibroids, both conditions that have been shown to benefit from mifepristone therapy. However, the use of mifepristone in contraceptive preparations that are widely available would pose an additional problem of possible misuse of the compound, the reason for currently limiting access to mifepristone. However, such risk should be easily avoidable in the case of postcoital contraception in which only one dose of mifepristone is needed. Regarding the future of mifepristone, and more broadly that of antiprogestins in contraception, the authors believe that they will have a place in the future contraceptive armament. As already emphasized, the strongest clinical areas are those of immediate postcoital and endometrial contraception. Additional studies evaluating parenteral modes of administration, the long-term endometrial effects, and safety and metabolic effects of prolonged antiprogestin administration are needed before mifepristone can be considered a part of the contraceptive arena.

Contraceptive Agents↗

PubMed1996

Inability to establish ectopic endometrium in a natural killer cell-deficient murine model. Immunologic, histologic and histochemical assessment.

OBJECTIVE: To investigate what effect natural killer (NK) cells have on the implantation of heterologous endometrial scrapings. STUDY DESIGN: Anti-asialo GM1 (AA-GM1) anti-sera have been shown to eliminate NK cell activity in various strains of rats and mice. Either AA-GM1 antibodies (+) or rabbit antiglobulin (-) was administered to beige mice (NK cell deficient) or beige control mice (not NK cell deficient of the same strain). The heterologous endometrial scrapings were prepared by scraping seven pairs of uterine horns from normal mice of the same strain. Beige and normal mice were then injected intraperitoneally every 3 days with the heterologous endometrial scraping and antibodies for a period of 50 days. The four experimental groups (n = 10 per group) can be summarized as being beige (+), beige (-), normal (+) and normal (-). RESULTS: There was no evidence of ectopic endometrial tissue in any of the four test groups by histologic examination or by using immunohistochemical staining techniques. Histologic evidence of an impaired immune response was clearly demonstrated in the beige mice receiving AA-GM1 antibodies. CONCLUSION: Using this model, a deficiency of NK cell activity did not appear to enhance the implantation of endometrial tissue on the abdominal peritoneum of mice.

Animals↗

PubMed1995

Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone.

OBJECTIVE: The pharmacokinetics of a 100 mg vaginal progesterone suppository was evaluated on days 1 and 7 and a 200 mg suppository on day 14. All the volunteers were given oral 17 beta-estradiol during the study. STUDY DESIGN: Ten postmenopausal women volunteered for this study. Progesterone was given as a vaginal suppository. Peripheral venous samples were obtained at appropriate intervals and analyzed for 17 beta-estradiol and progesterone levels. Area under the curve for progesterone was assessed by the trapezoidal method. Statistical analysis was performed by a one-way analysis of variance. RESULTS: Serum 17 beta-estradiol levels ranged from 22 to 182 pg/ml. Maximal serum progesterone levels ranged from 5.7 to 20.9 ng/ml, with the mean maximal levels 13.97, 16.09, and 12.68 ng/ml (not significantly different) and a mean area under the curve of 168.13, 207.64 and 227.71 ng/ml per hour on days 1, 7, and 14 (not statistically different). CONCLUSIONS: These data indicate that vaginal absorption of progesterone is efficient. The lack of difference in the area under the curve for both doses suggests that the vaginal mucosa or the total surface area of the vagina may limit the absorption of progesterone from the vagina.

Absorption↗

PubMed1995

Lea's Shield: a phase I postcoital study of a new contraceptive barrier device.

Lea's Shield is a new vaginal barrier contraceptive that may offer advantages over existing methods. It is made of silicone which is resistant to petroleum-based lubricants, does not absorb odors, and does not cause allergic reactions in users with latex sensitivity. It has an anterior loop for ease of insertion and removal and a one-way flutter valve. Its novel design has sufficient volume to fill the posterior fornix, which helps keep it in place and prevent sperm from entering the cervical os. This study evaluated with a standard postcoital test (PCT) the ability of the Lea's Shield used with spermicide or non-spermicidal lubricant to prevent sperm from entering midcycle cervical mucus. Ten sterilized women underwent four PCT cycles: one cycle in which no contraceptive barrier was used (a baseline cycle) and 3 cycles in which one of the following was used: Lea's Shield with spermicide, or with non-spermicidal lubricant, or the contraceptive diaphragm used with spermicide. All volunteers demonstrated more than 5 progressively motile sperm per high power field in the cervical mucus after intercourse in the baseline cycle. No motile sperm were found in the cervical mucus in any cycle in which Lea's Shield or the diaphragm was used with spermicide. No motile sperm were found in cervical mucus in 9 of 10 cycles in which Lea's Shield was used without spermicide. Only two progressively motile sperm were present in the cervical mucus of one volunteer who used the shield with non-spermicidal lubricant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

The effect of progesterone on the accumulation of leukocytes in the human endometrium.

OBJECTIVE: Our purpose was to determine the role of progesterone on the number and type of leukocytes found in human endometrium. STUDY DESIGN: Endometrial tissue was obtained from normally cycling women and from women receiving hormone replacement therapy for premature ovarian failure. All tissues were formalin fixed, sectioned, and stained with specific antibodies to leukocytes, T cells, B cells, and macrophages. Each tissue was also dated by means of published techniques. Quantitation was performed by counting all immunopositive cells in five high-powered fields. Data were compared by analysis of variance and Mann-Whitney U test. RESULTS: Leukocytes increased from 31.1 to 99.1 per high-powered field (p = 0.0001), and T cells increased from 10.9 to 20.4 per high-powered field (p = 0.001) after 12 days of progesterone treatment of women with ovarian failure. Normally menstruating women in the late luteal phase had similar concentrations. Neither B cells nor macrophages were found to increase with progesterone treatment. CONCLUSIONS: These data indicate that progesterone results in an increased leukocyte and T-cell concentration in human endometrium.

Adult↗

PubMed1994

Clinical and metabolic features of desogestrel: a new oral contraceptive preparation.

Desogestrel is a highly selective gonane progestin. A monophasic formulation containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol has recently been approved as an oral contraceptive (OC) in the United States. Although desogestrel-containing formulations are new to the United States, they have been the most widely prescribed OCs in Europe for almost 10 years. An extensive literature demonstrates that desogestrel-containing preparations are safe, effective, and well tolerated by most women. In light of desogestrel's high selectivity, low affinity for androgen receptors, and lack of interference with the increase in sex hormone-binding globulin, desogestrel-containing OCs may be particularly appropriate for women with androgen-induced skin disorders because of their high selectivity. Several European studies have found significant improvement or almost complete resolution of previously existing acne. Desogestrel provides excellent cycle control, no major impact on weight, minimal or no adverse effects on blood pressure, statistically significant increases in high-density lipoprotein cholesterol with low-density lipoprotein cholesterol usually unchanged or reduced, and little effect on glucose tolerance or insulin resistance.

Acne Vulgaris↗

PubMed1994

Pharmacokinetics of a triphasic oral contraceptive containing desogestrel and ethinyl estradiol.

OBJECTIVE: To demonstrate that pharmacokinetic measurements were made at steady state. Subsequently, dose proportionality for desogestrel and ethinyl E2 kinetics were demonstrated. DESIGN: Open-label, noncomparative study. SETTING: Healthy volunteers in an academic research environment. PARTICIPANTS: Twenty white women who were 19 to 32 years old were solicited via an advertisement. Nineteen of the 20 women completed the study. INTERVENTIONS: Study medication consisted of three cycles of a triphasic oral contraceptive containing desogestrel and ethinyl E2. Blood samples were taken at baseline and during cycle 3 between -48 and 24 hours on days 1, 7, 14, and 21, with additional sampling times on day 21 at 48, 60, and 72 hours. MAIN OUTCOME MEASURES: Serum concentrations of 3-keto-desogestrel and ethinyl E2. RESULTS: Evaluation of the trough serum levels indicated that a steady state of 3-keto-desogestrel had been reached. Statistical analysis on the Cmax, area under the curve (AUC), and Css,min indicated dose proportionality for the administered desogestrel. Ethinyl E2 serum levels obtained at the same time points also reflected steady state levels and showed minimal variability. The statistical analysis on Cmax, AUC, Css,min, and Tmax indicated that the pharmacokinetics of ethinyl E2 on days 7, 14, and 21 were not statistically significantly different, indicating dose equivalency. CONCLUSIONS: Steady state of 3-keto-desogestrel is reached after each of the three phases and the pharmacokinetics are dose proportional. After reaching steady state, the pharmacokinetics of ethinyl E2 remain constant over time.

Adult↗

PubMed1994

The influence of pentoxifylline (Trental) on the antifertility effect of intrauterine devices in rats.

OBJECTIVE: To test the hypothesis that the inflammatory response stimulated by intrauterine devices (IUDs) plays a role in the antifertility action of IUDs. We treated rats with pentoxifylline (Trental; Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) and evaluated its effect on the anti-implantation action of IUDs. The number of embryos in treated compared with untreated rats was determined. DESIGN: Breeder female Sprague-Dawley rats (Harlan Sprague Dawley, Indianapolis, IN) were randomized into one of five test groups (n = 20 per group). A monofilament nylon IUD was inserted transcervically into one horn of the bicornuate uterus in two groups. The IUD-bearing groups received either intraperitoneal (IP) injections of pentoxifylline (45 mg/kg per every 12 hours) or normal saline (NS). The two non-IUD-bearing groups received IP injections of pentoxifylline or NS. The non-IUD group was not injected. All injections were administered daily for 21 days and the animals then mated. Successful mating was determined by the presence of spermatozoa in vaginal washings. The injections of pentoxifylline or NS were continued until day 12 of pregnancy when the rats were killed. The total number of embryos in each uterine horn was determined. SETTING: University research laboratory. RESULTS: Embryo numbers (1.0 +/- 0.6 [mean +/- SEM]) were reduced in the IUD horn compared with the contralateral non-IUD horn (6.4 +/- 1.0) and with the uterine horns from each of the four other test groups. The number of embryos were increased in the IUD horn (3.5 +/- 0.9) of the pentoxifylline-treated rats. CONCLUSION: Pentoxifylline appeared to reduce the contraceptive effectiveness of the IUDs in this model.

Animals↗

PubMed1994

Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group.

OBJECTIVE: To compare the bleeding patterns obtained with two continuous combined and two sequential regimens of conjugated estrogens with medroxyprogesterone acetate (MPA) and conjugated estrogens alone. METHODS: This was a 1-year double-blind, randomized study done with 1724 postmenopausal women at 99 sites in the United States and Europe. All five treatment groups received 0.625 mg/day of conjugated estrogens. Groups A and B also took continuous daily doses of 2.5 and 5.0 mg of MPA, respectively. Groups C and D took 5.0 and 10.0 mg of MPA, respectively, for the last 14 days of each 28-day cycle. Group E took continuous daily doses of placebo to match MPA. RESULTS: The two continuous combined regimens (A and B) produced amenorrhea in 61.4 and 72.8%, respectively, of all evaluable cycles. Generally, the incidence of amenorrhea increased and irregular bleeding decreased with longer duration of treatment. In addition, amenorrhea occurred for at least the last seven consecutive cycles of the treatment year for about 40% of the patients taking the lower-dose continuous combined regimen (A), about 50% of the patients taking the higher-dose continuous combined regimen (B), and about 50% of the patients taking conjugated estrogens alone. About 5% of the patients who took either of the sequential regimens (C or D) had amenorrhea during that time. Most of the cycles (81.3 and 77.0% in groups C and D, respectively) for patients taking the sequential conjugated estrogens-MPA regimens had regular withdrawal bleeding or withdrawal spotting. There was no bleeding or spotting in 75.5% of the cycles for patients who took conjugated estrogens alone. CONCLUSIONS: Approximately half of the women who took the continuous combined conjugated estrogens-MPA regimens had amenorrhea, and the incidence tended to increase during the study. Women who took the sequential regimens had good cycle control with minimal irregular bleeding. More than half of those who took conjugated estrogens alone had amenorrhea.

Adult↗

PubMed1993

Tissue response to bioerodible, subcutaneous drug implants: a possible determinant of drug absorption kinetics.

The fibrous tissue compartments that develop in response to the subcutaneous implantation of bioerodible heat-fused rods of norethindrone and cholesterol (85 and 15%, respectively) were studied by light and electron microscopy at various intervals after implantation to determine whether the biological inflammatory response may play a role in drug absorption. Thirty-five regularly menstruating, sterilized (tubal ligation), healthy females each received four Annuelle rods. The microanatomy of seven of the largest implants (135 mg norethindrone) was studied. A dense fibrous biological compartment was found to surround each rod. By light microscopy no abnormal tissue response was revealed. Scanning and transmission electron microscopy showed that the surfaces of the rods were covered by a cellular matrix of mononuclear cells. The fibrous compartment was composed of a loose cellular bed immediately surrounding the norethindrone rod, a dense fibrous connective tissue envelope containing blood and lymphatic vessels, and an outer fatty connective tissue layer. Transmission electron microscopy confirmed that the cellular tissue immediately surrounding the rods was composed mainly of lipid laden macrophages. Norethindrone levels in tissue capsules at 3 and 10.5 months were 0.05 and 8.4% by weight, respectively. These observations suggest that the local inflammatory response plays a role in the active processing of this delivery system. This picture is qualitatively different from the general view of the fibrous capsule as a simple rate limiting membrane. The effects observed in this study suggest that a more complex, functional biological system develops in response to the subcutaneous introduction of a drug delivery device.

Absorption↗

PubMed1993

Peritoneal fluid: its relevance to the development of endometriosis.

OBJECTIVE: To review and evaluate published studies that have examined the role of peritoneal fluid (PF) in the development of endometriosis. DESIGN: Important studies related to this topic have been identified through a computerized bibliographical search (MEDLINE), as well as by manually scanning the published literature of major reproductive journals over the last several years. MAIN OUTCOME MEASURES: Studies that examined the effect of PF or its components on the pathophysiology of endometriosis are discussed. These include reported effects on the histogenesis, maintenance and proliferation of endometriosis, as well as related actions on infertility. RESULTS: The majority of investigations into the role PF plays in the pathogenesis of endometriosis have evaluated how it may adversely affect fertility. Suggestive but inconclusive data in the literature indicate that degenerating endometrial tissue may release a biochemical factor(s) into the peritoneal environment that is capable of inducing ectopic endometrium formation. Peritoneal fluid itself contains growth factor that may play a role in the implantation and maintenance of the ectopic endometrium. CONCLUSIONS: The PF of women with endometriosis has been shown to contain angiogenic as well as other growth factors. These compounds may contribute to the proliferation of the ectopic endometrium.

Ascitic Fluid↗

PubMed1992

Effects of chronic nocturnal opiate antagonism on the menstrual cycle.

OBJECTIVE: Opioids generally suppress gonadotropin secretion. We investigated whether chronic opiate antagonism would affect the occurrence or timing of menstrual cycle events. STUDY DESIGN: Opiate blockade was maintained in nine normal volunteers from cycle days 1 through 13 with naltrexone. A double-blind, placebo-controlled crossover design was used. Serum estradiol and progesterone were measured daily. Vaginal ultrasonography was performed daily beginning cycle day 10. Endometrial biopsies were performed 10 to 12 days after ovulation. Nonparametric paired data analysis was used. RESULTS: No significant differences in the following menstrual cycle parameters were detected between naltrexone and placebo cycles: cycle length (25.4 +/- 0.9 vs 25.7 +/- 0.5 days), maximum follicle size (21.5 +/- 1.0 vs 20.8 +/- 1.1 mm), peak serum progesterone (15.8 +/- 1.8 vs 15.2 +/- 2.2 ng/ml), or integrated serum progesterone (108.1 +/- 12.8 vs 101.2 +/- 14.6 ng/ml/day). Histologic endometrial development was normal in all subjects during naltrexone cycles. CONCLUSION: These data suggest that naltrexone-suppressible opioid activity does not play a significant role in the regulation of follicular events in normal women.

Adult↗

PubMed1992

Reversible contraception for the woman over 35 years of age.

Methods of reversible contraception, oral contraceptives, intrauterine devices, and Norplant (systemic progestin-only contraceptive; Wyeth-Ayerst, Radnor, PA), can be used for women over 35 years of age. Oral contraceptive formulations are safe and effective for healthy women up to the age of menopause. Oral contraceptives in women who do not smoke cigarettes do not result in a significant increased risk for cardiovascular disease. The incidence of breast cancer is not increased in women who have used oral contraceptives. A slight increase was found in younger women who had been on oral contraceptives based on a reanalysis of the contraceptive and steroid hormone study of the Centers for Disease Control. A reduction in the incidence of ovarian epithelial neoplasia by 40% was found in three European case-control studies. Two intrauterine devices are currently available on the US market: Paragard (GynoPharma, Somerville, NJ) and Progestasert (Alza Corp., Palo Alto, CA). Both of these provide highly effective contraception. A World Health Organization prospective randomized study found that there was an increase in pelvic inflammatory disease rates in the first 20 days after intrauterine device insertion. The intrauterine device itself did not increase the pelvic inflammatory disease incidence rates. The Norplant system exerts its contraceptive action through ovulation inhibition and alteration of cervical mucus. The major consumer complaint is irregular or prolonged uterine bleeding, which can be controlled by oral estrogen.

Adult↗

PubMed1991

Endometrial morphology in asymptomatic postmenopausal women.

Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women.

Adult↗

PubMed1991

Studies on the in vitro spermicidal activity of synthetic magainins.

Two synthetic magainins A and G are shown to have spermicidal activity. Transmission electron microscopic micrographs show that both magainins alter the plasma membranes of sperm and that these actions are rapid. Further studies will better delineate the contraceptive potential of synthetic magainins.

Antimicrobial Cationic Peptides↗

PubMed1991

Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol.

The pharmacokinetics of three transdermal estradiol (E2) replacement regimens were studied following establishment of steady-state dynamics. Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm transdermal delivery system 4 mg (0.05 mg/day) were administered for 14 days each to 15 postmenopausal volunteers, with a 14-day washout period between each regimen. The percutaneous E2 pharmacokinetics were compared with an oral micronized E2 preparation. Venous samples were obtained at 0, 1, 2, 4, 8, 12, and 24 hours on 3 sequential days 11 days after initial application of the Oestrogel and the transdermal delivery system, and at the same times after oral E2 ingestion. All three percutaneous regimens provided nearly constant serum E2 and estrone (E1) levels throughout their use. The mean serum E2 levels were 102.9 +/- 39.9, 68.1 +/- 27.4, and 41.1 +/- 13.5 pg/mL for Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm, respectively. Oral E2 resulted in a mean serum E2 level of 114.0 +/- 65.2 pg/mL with marked peak and nadir values. The E1/E2 ratio was comparable with all three percutaneous regimens (1.08-1.33) and was significantly lower than that found with oral Estrace (5.05).

Administration, Cutaneous↗

PubMed1990

Uterine endometrial peristalsis--a transvaginal ultrasound study.

Peristaltic movements of the endometrium were evaluated by serial transvaginal ultrasound throughout 21 spontaneous menstrual cycles, 15 oral contraceptives (OCs) cycles, and 18 in vitro fertilization (IVF) cycles. A score of 0, 1, or 2 was assigned for absent, mild, or strong movements. An average score of 1.5 was obtained at midcycle in spontaneously ovulating women, which was significantly different from early or late follicular (0.36 and 0.5) or luteal (0.4) phase scores. Significant differences were found among the three groups: IVF patients averaged more movements than natural cycle patients, who in turn had a higher incidence than patients taking OCs. Increased peristaltic endometrial movements appear to occur in women around midcycle, probably as an enhancing mechanism for sperm propulsion towards the tubal ostia.

Adult↗