Misoprostol and pregnancy.
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Abortifacient Agents, Nonsteroidal↗
Biomedical subjects
P D Darney
Publications and source records attributed to P D Darney.
Effects of a monthly injectable steroidal contraceptive, Mesigyna, on menstrual pattern, lipoproteins, and coagulation parameters.
The objective of this study was to determine the effects of a once-monthly injectable contraceptive (Mesigyna) on menstrual pattern, lipoproteins, and coagulation parameters. Thirty-six women aged 18-35 years requesting monthly injectable contraception were included. Before injecting estradiol valerate 5 mg and norethisterone enanthate 50 mg, coagulation, lipoprotein, and liver function parameters were determined. After the 3- and 6-month injections, the same coagulation and serum lipid measurements and liver function tests were repeated, and women were questioned about their menstrual patterns and side effects. Thirty women who completed 6 months were evaluated. At the end of 3 months, two-thirds of the 30 women had normal menstrual patterns; at the end of 6 months, 80% of the women had normal menses. Serum LDL, total cholesterol, and triglyceride levels did not change significantly, while HDL and VLDL decreased significantly (p = 0.032 and p = 0.039, respectively) at 6 months. PT and aPTT measures did not change at the end of 6 months, while fibrinogen levels were significantly lower (p = 0.013). Serum total bilirubin levels increased (p = 0.022) and albumin levels decreased (p = 0.022) at the end of 6 months. Mesigyna was well tolerated and side effects and menstrual abnormalities were acceptable. There were no clinically significant changes in lipoprotein, coagulation, or hepatic parameters.
Adolescent↗
Digoxin to facilitate late second-trimester abortion: a randomized, masked, placebo-controlled trial.
OBJECTIVE: To examine the efficacy of digoxin for decreasing operative time, difficulty, and pain of late second-trimester surgical abortions. METHODS: We performed a randomized, double-masked, placebo-controlled trial of intra-amniotic digoxin for second-trimester dilation and evacuation (D&E) involving 126 consecutive women at an inner-city public hospital. Eligible women had gestational ages of 20-23.1 weeks, spoke English or Spanish, and were at least 16 years old. Digoxin (1 mg) or saline was injected intra-amniotically 24 hours before the procedure, at cervical laminaria insertion. The primary outcome was procedure duration. Sample size was based on 80% power to detect a difference of 3.5 minutes between groups. RESULTS: The two groups were similar in demographic factors, obstetric histories, and gestational duration. The average gestational length was 22.5 weeks. There was no difference in procedure duration (mean +/- standard deviation) between groups (placebo 14.7 +/- 7.0, digoxin 15.4 +/- 8.0). There were no differences in blood loss estimated by surgeons, pain scores, procedure difficulty scores, or complications between groups. Vomiting was significantly more common in those who received digoxin (placebo 3.1%, digoxin 16.1%). Most subjects (91%) reported that they preferred their fetuses were dead before the abortions. CONCLUSION: Although digoxin did not increase efficacy of late second-trimester abortion, patient preference might justify its use.
Abortifacient Agents↗
Implantable contraception.
Although levonorgestrel contraceptive implants have been available for over 15 years, innovations have only recently led to a wider choice. These new implants offer easier insertion and removal and other advantages depending on the type of progestin. Implants prevent pregnancy by several mechanisms, including inhibition of ovulation and luteal function and alteration of cervical mucus and the endometrium. The high efficacy and ease of maintenance make implants an ideal contraceptive for many women, including adolescents, a population that uses implants infrequently but reports high satisfaction. Implants are appropriate for women who are breastfeeding, who have contraindications to estrogen, or who have diseases such as diabetes, hypertension, sickle cell anemia, or an HIV infection because implants have few metabolic or hematologic effects. Long-term use has not been associated with a decrease in BMD and generally leads to increased blood levels and iron stores. Women who wish to space their pregnancies appreciate the nearly immediate onset of action with insertion and the rapid termination of all effects with removal. All types of implants lead to menstrual changes and other side effects in some women. Adverse effects that occur in implant users more than the general population include headaches and acne. Women must be thoroughly counseled regarding the potential for menstrual alteration, side effects, and sexually transmitted infections if they do not use condoms. Despite their initial high cost, implants are a cost-effective method over several years, even when discontinued before the life of the implant.
Adolescent↗
Safety of intra-amniotic digoxin administration before late second-trimester abortion by dilation and evacuation.
OBJECTIVE: The purpose of this study was to determine the safety of intra-amniotic digoxin injection before late second-trimester pregnancy termination by dilation and evacuation through an assessment of maternal systemic digoxin absorption, cardiac rhythm, and coagulation parameters. STUDY DESIGN: Pregnant women at between 19 and 23 weeks' gestation received 1.0 mg digoxin through intra-amniotic injection and then had serum digoxin levels determined for 48 hours and Holter cardiac monitoring performed for 24 hours. Clotting parameters were assessed before digoxin injection and 24 hours later, at the time of the dilation and evacuation procedure. RESULTS: Eight patients completed the study. The mean (+/-SD) serum digoxin peak concentration was 0.81 +/- 0.22 microg/L (range, 0.5-1.1 microg/L). The mean (+/-SD) time to peak digoxin concentration was 11.0 +/- 5.55 hours (range, 4-20 hours). Ambulatory cardiac monitoring showed no rhythm or conduction abnormalities associated with digoxin. Prothrombin time, partial thromboplastin time, and fibrinogen levels did not change significantly between determinations before and after the dilation and evacuation procedure (11.5 to 11.4 seconds, 24.1 to 24.4 seconds, and 441 to 475 mg/dL, respectively). CONCLUSION: The maximum digoxin concentration peak achieved after intra-amniotic injection was in the low therapeutic range. No rhythm or conduction abnormalities associated with digoxin were noted by Holter monitoring. Coagulation parameters did not change significantly. On the basis of the limited systemic absorption and the absence of clinically significant cardiac or clotting effects, intra-amniotically administered digoxin may be considered safe for use before late second-trimester pregnancy terminations.
Abortion, Induced↗
Ovarian steroid and cytokine modulation of human endometrial angiogenesis.
A key mechanism underlying the cyclical growth of the endometrium is its ability to regenerate a vascular capillary network. In normal cycling human endometrium, angiogenesis is influenced by both endocrine and paracrine factors. Hormonal manipulation of the endometrium, such as that occurring during the use of steroidal contraception, appears to result in capillary proliferation and fragility. As a consequence of these vascular changes, contraceptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In this paper we address mechanisms responsible for vascular endothelial cell proliferation in normal and contraceptive steroid-exposed endometria. We propose that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial stromal cells is increased by oestrogens and progestins. Three proinflammatory cytokines with angiogenic effects in other systems (i.e. interleukin-1beta, tumour necrosis factor-alpha and interferon-gamma) do not appear to up-regulate VEGF expression in normal endometrial stromal cells. Well-characterized in-vitro models in conjunction with immunohistochemistry provide useful experimental systems to study endometrial neovascularization under physiological conditions and in those potentially perturbed via the use of contraceptive steroids.
Biopsy↗
Implantable contraception.
This article reviews the advantages and disadvantages of progestogen-only contraceptive implants in light of the development of Implanon, a new, single-rod, etonogestrel-releasing system. Implants rapidly produce serum progestogen levels sufficient to ensure contraception for 1-5 years. The steady release ofprogestogen avoids the peaks and troughs associated with oral contraceptives, the profound ovarian suppression observed with depot injections and the need for user compliance. Implants have few serious complications. Ectopic pregnancy rates are low, and follicular hypertrophy is generally self-limiting. The principal acceptability limitation to both users and providers of Norplant is insertion and removal. Implanon is easy to insert and remove with minimal complications and pain. The main adverse event causing discontinuation of implants is a change in bleeding pattern. However, with good counselling, this is well tolerated by most women. Implants thus provide an effective, safe, economical and convenient alternative to oral, injectable or intrauterine contraceptives. Implanon is an extremely effective single-rod implant with a Pearl index of 0. It employs a new polymer and a less androgenic progestogen. These features provide easier insertion and removal for both users and clinicians, a more stable release rate and potentially fewer adverse androgenic effects compared with existing formulations.
Contraceptive Agents, Female↗
Condom practices of urban teens using Norplant contraceptive implants, oral contraceptives, and condoms for contraception.
OBJECTIVES: The availability of long-acting hormonal birth control methods has created new contraceptive options for adolescents. The purpose of this study was to determine whether teens initiating these methods use condoms less frequently than teens using oral contraceptive pills or condoms alone and may therefore be at an increased risk of acquiring sexually transmitted infections. STUDY DESIGN: To investigate ongoing condom behavior in teens using levonorgestrel (Norplant) contraceptive implants, oral contraceptives, and condoms alone, we examined data from a 2-year prospective cohort study of 399 urban teens. The study consisted of 3 clinic-based cohorts of adolescent female contraceptive users: Norplant contraceptive implants (n = 200), oral contraceptives (n = 100), and condoms alone (n = 99). Data were collected at an admission interview and at 1- and 2-year follow-up from method continuers. RESULTS: Norplant contraceptive implant users were less likely than oral contraceptive or condom users to report condom use at last sex or consistent condom use at 1- and 2-year follow-up. The implant group showed a significant decrease in condom use from admission to 2 years after method initiation. The proportion of implant users self-reporting new sexually transmitted infections at 2-year follow-up, however, was not significantly greater than that of oral contraceptive or condom users. CONCLUSIONS: Our findings indicate that teen users of Norplant contraceptive implants are less likely to use condoms than teens who choose oral contraceptives but, probably because of differences in sexual behavior, are no more likely to self-report sexually transmitted infections. Our findings also indicate that teens who choose oral contraceptives and condoms do not use them consistently enough to avoid pregnancies or sexually transmitted infections.
Adolescent↗
Absorption kinetics of misoprostol with oral or vaginal administration.
OBJECTIVE: To compare the pharmacokinetics of vaginal and oral administration of the prostaglandin E1 analogue, misoprostol. METHODS: Twenty women received 400-micrograms doses of misoprostol either orally or as tablets placed in the vagina. Serum levels of principal metabolite, misoprostol acid, were measured at 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes. The first ten women were pregnant and undergoing first-trimester abortions, and the last ten were not pregnant and had additional blood sampling at 360 minutes. We compared the pharmacokinetics of misoprostol acid after oral and vaginal administration. RESULTS: All 20 subjects completed the study. The maximum mean (+/- standard deviation [SD]) of misoprostol acid differed significantly between the oral and vaginal groups (277 +/- 124 compared with 165 +/d- 86 pg/mL, respectively; P = .03, analysis of variance), as did the mean +/- SD time to peak levels (34 +/- 17 compared with 80 +/- 27 minutes, respectively; P < .001) and areas under the misoprostol concentration versus time curve (mean +/- SD) up to 4 hours (n = 20,273.3 +/- 110.0 compared with 503.3 +/- 296.7 pg.hour/mL, respectively; P = .033) and up to 6 hours (n = 10, 300.0 +/- 103.3 compared with 956.7 +/- 541.7 pg.hour/mL, respectively; P = .029). The extent of absorption was highly variable among subjects in each group. CONCLUSION: There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and oral routes that may explain the difference observed in clinical efficacy. Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma, our observation of the prolonged serum concentrations in the vaginal group suggests that vaginal administration could be dosed at longer intervals than oral.
Abortifacient Agents, Nonsteroidal↗
Medical abortion with oral methotrexate and vaginal misoprostol.
OBJECTIVE: To evaluate the safety and efficacy of oral methotrexate and vaginal misoprostol for medical abortion. METHODS: A prospective multicenter trial involved 300 women up to 49 days' gestation seeking elective abortion. Subjects received methotrexate 50 mg orally followed 5-6 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated if abortion did not occur. RESULTS: Complete abortion occurred in 273 of 299 women (91.3%; 95% confidence interval [CI] 87.5, 94.2%); one woman was lost to follow-up. Abortion occurred within 8 days of the methotrexate in 233 women (77.9%; 95% CI 72.8, 82.5%); the remaining 13.4% of women who aborted did so after a delay of 23.5 +/- 9.8 days (median 23 days, range 10-45). Vaginal bleeding lasted an average of 15 and 11 days in immediate and delayed-success abortions, respectively. Complete abortion rates decreased linearly with increasing body surface area. After methotrexate and misoprostol administration, nausea was reported in 37% and 33%, vomiting in 11% and 18%, diarrhea in 12% and 18%, and subjective fever or chills in 15% and 31% of subjects, respectively. CONCLUSION: Oral methotrexate followed by vaginal misoprostol is effective for abortion and represents an acceptable alternative to intramuscular methotrexate in regimens for medical abortion.
Abortifacient Agents, Nonsteroidal↗
OC practice guidelines: minimizing side effects.
The side effects of oral contraceptives (OCs) can be minimized by appropriate OC selection. Side effects or perceived side effects that manifest themselves physically--e.g., weight gain, breakthrough bleeding (BTB), nausea, headache, breast tenderness, mood swings, acne, and hirsutism--are the most common causes of premature discontinuation of oral contraception. The relative androgenicity of the progestin component of combination OCs has become an important differential in selecting OC formulations. Several studies have indicated that preparations with less androgenic potential can minimize some of the "physical" side effects and adverse metabolic effects traditionally associated with oral contraception. Acne and hirsutism, common pre-existing conditions that are clearly related to the androgenicity of the progestin component, can be eliminated or improved by use of OCs with low androgenic activity. Many women perceive that OCs cause weight gain; although weight gain is to some extent androgen related, most studies comparing low-androgenic OCs with medium- or high-androgenic preparations have found little or no change in weight regardless of formulation. BTB, which usually subsides within a few months, is related to the dose, potency, and ratio of the estrogen and progestin in the OC formulation. Low-estrogen-dose OCs (< or = 35 micrograms ethinyl estradiol [EE]) containing less androgenic progestins are associated with bleeding patterns as acceptable as older low-estrogen-dose formulations. The same analysis found that smoking cigarettes promotes BTB in women who use OCs. There is no convincing evidence that the use of one progestin or another is less likely to cause or exacerbate headache; however, changing preparations sometimes reduces the incidence. Women with persistent headaches during the pill-free interval may benefit from a longer cycle of OC treatment. Nausea and breast tenderness are primarily estrogen-related effects; if a women experiences persistent nausea, switching to an OC formulation containing 20 micrograms EE may be appropriate as long as the patient is cautioned that BTB is more likely. Mood changes are a common, highly subjective complaint whose relationship to OC use is hard to assess. Concerns about the potentially deleterious effects of combination OCs on lipid/lipoprotein and carbohydrate metabolism have been substantially diminished by new epidemiologic findings relative to cardiovascular disease as well as by the development of low-androgenic progestins. Formulations containing these progestins lower LDL cholesterol and increase HDL cholesterol; they do not affect carbohydrate metabolism as much as older, more androgenic formulations.
Adolescent↗
Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users.
The objective of this study was to determine the relevance of serum estradiol, progesterone and levonorgestrel concentrations to endometrial histology and uterine bleeding associated with long-term Norplant implants use. Eighteen five-year users of Norplant implants had endometrial biopsies and determinations of serum estradiol, progesterone and levonorgestrel concentrations. Correlations among these factors and uterine bleeding were calculated. Proliferative endometrium (but not sex steroid levels) was associated with abnormal bleeding. Neither ovarian steroid nor levonorgestrel concentrations was a predictor of abnormal bleeding. Hyperplastic changes were not seen even with high estradiol and low levonorgestrel levels.
Adult↗
Methotrexate and misoprostol for early abortion: a multicenter trial. I. Safety and efficacy.
A prospective trial was conducted including 300 pregnant women seeking elective abortion to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 56 days gestation. Subjects received methotrexate 50 mg/ m2 intramuscularly followed 7 days later by misoprostol 800 micrograms vaginally. The misoprostol dose was repeated the next day if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), duration of vaginal bleeding, and side effects. Complete abortion occurred in 263/ 300 (87.7%, 95% CI 83.4, 91.2%) patients. The complete abortion rate was higher for early gestations: 183/202 (90.6%, 95% CI 85.7, 94.2%) at < or = 49 days gestation, and 80/98 (81.6%, 95% CI 72.5, 88.7%) from 50-56 days gestation (p = 0.038). Abortion occurred in the 24 hours following the initial or repeat misoprostol dose (immediate success) in 65.0%; the remaining 22.7% of women who aborted did so after a delay of 23.6 +/- 9.1 (mean +/- standard deviation) days. Vaginal bleeding lasted 14 +/- 7 days and 11 +/- 9 days in immediate success and delayed success patients, respectively. Overall, 69.7%, 87.7%, and 91.7% of patients had passed the pregnancy by 14, 28, and 35 days, respectively, after receiving methotrexate. Methotrexate and misoprostol side effects were minimal. This treatment regimen offers an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.
Abortifacient Agents, Nonsteroidal↗
Combination oral contraceptives and cardiovascular disease.
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Arteriosclerosis↗
The androgenicity of progestins.
All steroid hormones are structurally similar, but relatively minor differences cause profound alterations in biochemical activity. The 21-carbon series (pregnane nucleus) includes the corticoids and the true progestins (e.g., medroxyprogesterone acetate). The 19-carbon series (androstane nucleus) includes all the androgens, among them the progestins used in most oral and parenteral contraceptives. The removal of carbon 19 from testosterone changes the major hormonal effect from androgenic to progestogenic, but these "19-nor" steroids retain varying degrees of androgenic activity. (They can also have limited estrogenic activity, but this is insignificant at the low doses used for contraception.) Some of the 19-nortestosterone progestins are metabolized to other compounds (e.g., norethynodrel, ethynodiol diacetate, and lynestrenol to norethindrone), and some (levonorgestrel, desogestrel) are active unchanged. The lingering androgenic effects of 19-nor progestins are dose-related, opposed by estrogen, and are manifested metabolically (e.g., glucose tolerance, lipoprotein synthesis) and symptomatically (e.g., acne, weight gain). The effect of 19-nortestosterones on lipoproteins prompted the development of less androgenic compounds, but the obvious benefit of the new progestins (desogestrel, gestodene, norgestimate) is a reduction in the symptoms associated with the androgenicity of the older compounds. Mitigation of androgenic effects on lipoprotein and carbohydrate metabolism could have long-term benefits, especially for women who are at risk of arteriosclerotic vascular disease; however, these effects remain to be epidemiologically demonstrated.
Androgens↗
Hormonal implants: contraception for a new century.
Subdermal implants are contraceptive systems that release low, stable amounts of synthetic progestins from Silastic or other materials for periods of months to several years. Unlike other hormonal delivery systems, they do not cause unnecessary peaks in progestin levels and do not use estrogens, and thus their health risks are minimal. Norplant has been studied more extensively than any other subdermal contraceptive implant. More than 60,000 women have participated in clinical trials, which demonstrated that this approach is one of the most effective reversible contraceptive methods available (1% pregnancy rate in 5-year users). The implant also reduces the incidence of ectopic pregnancy to a level much below noncontraceptive users and about equivalent to TCu380A intrauterine device users. Exposure to the sustained, low dose of levonorgestrel delivered by Norplant has shown only minor metabolic changes. Side effects are minor but often bothersome, causing some discontinuation of the method. First-year continuation rates range from 76% to 90%. Fertility return after discontinuation is prompt. Difficulty in removal of the implant capsules by the less experienced practitioner has motivated researchers to develop systems that are easier to use, less obvious under the skin, and biodegradable. The Norplant 2 system is faster, easier, and less painful to insert and remove. Implants under investigation release desogestrel and other progestins; Capronor and subdermal norethindrone pellets are biodegradable systems.
Contraceptive Agents, Female↗
Methotrexate and misoprostol for early abortion.
Methotrexate is cytotoxic to trophoblast and, in low doses, has minimal side effects. It is used to treat both gestational trophoblastic neoplasia and ectopic pregnancy. The cytotoxic effects of methotrexate on intrauterine trophoblast should be equivalent. To test this hypothesis, ten pregnant women, < 8 weeks' gestation were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days later by misoprostol, a prostaglandin E1 analogue. The first 4 patients received misoprostol 600 micrograms orally; none aborted soon after the misoprostol. Two patients aborted 25 and 26 days after the methotrexate injection and two elected a suction abortion after 14 days (one by choice and one because the pregnancy was still viable). The last 6 patients received misoprostol 800 micrograms vaginally and aborted within 3-8 hours. One patient had an incomplete abortion requiring a suction curettage 34 days after the misoprostol. Vaginal bleeding for these 6 patients lasted an average of 29 +/- 11 days (range, 12-42 days). No methotrexate side effects were observed. Vaginal misoprostol (800 micrograms) was significantly more effective (p = 0.005) than oral misoprostol (600 micrograms) in effecting abortion after intramuscular methotrexate.
Abortion, Induced↗
Contraceptive choices for behaviorally disordered women.
Women with psychologic disturbances of depression, anxiety, or thought disorganization pose a special management problem when providing a safe and effective means of contraception. The difficulty is compounded by the fact that many mentally disturbed women also abuse drugs. Therefore, providing contraception to the many types of behaviorally disturbed women requires the full range of contraceptive options and protection from sexually transmitted diseases. When compliance can be assured, oral contraceptives are the preferred method. When compliance is questionable, progestin implants or injections may be tried. However, progestin-only preparations are associated with several side effects, including worsening of mood in depressive patients.
Contraception↗