Arbuscular mycorrhizae of the palm Astrocaryum mexicanum in disturbed and undisturbed stands of a Mexican tropical forest.

Tropical forests are dynamic systems with extensive natural disturbance, gaps in the canopy being one of the most important types. Tree and branch fall are often the principal cause of natural disturbance. This research was done on adult individuals of a very abundant palm ( Astrocaryum mexicanum Liebm, Arecaceae), which is found in the understorey of the forest at Los Tuxtlas, Mexico. Percentages of colonization by arbuscular mycorrhizae were determined for individuals selected randomly from plots located both in gaps and under closed canopy. The highest percentages of total colonization, as well as those of hyphae and vesicles, were recorded for gaps. In forest with closed canopy, arbuscules had the highest percentages of colonization; on these sites the palm has been observed to grow less. The higher production of arbuscules may favour nutrient capture in this microenvironment, which is characterized by strong competition.

Delayed first injection of the once-a-month injectable contraceptive containing 25 mg of medroxyprogesterone acetate and 5 mg of E(2)-cypionate: effects on ovarian function.

OBJECTIVE: To assess whether women who were administered the first injection of DMPA+E(2)C on day 7 of their menstrual cycle (delayed injection) exhibit the same degree of ovarian suppression as women who receive it on day 5 of their menstrual cycle. DESIGN: Multicenter, randomized controlled trial. SETTING: Reproductive health clinics. PATIENT(S): Women aged between 18 and 38 years (inclusive) willing to use DMPA+E(2)C as their method of contraception. INTERVENTION(S): Participants received a DMPA+E(2)C injection on day 5 (control group, n = 41) or day 7 (delayed-injection group, n = 117) of their menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian activity and follicular development determined by serial serum progesterone levels and vaginal ultrasound. RESULT(S): Participants who received DMPA+E(2)C on day 5 of their menstrual cycle (control group) exhibited no more than limited follicular growth (no follicle >16 mm). Of those women who received DMPA+E(2)C on day 7 of their menstrual cycle (delayed-injection group), 21 (18%) showed some follicular growth, of whom 4 (3%) ovulated. CONCLUSION(S): The first injection of DMPA+E(2)C given on day 7 of a menstrual cycle does not provide the same inhibition of ovarian activity as that observed when it is administered on day 5 of the menstrual cycle.

Delayed first injection of the once-a-month injectable contraceptive containing 25 mg medroxyprogesterone acetate and 5 mg estradiol-cypionate: effects on cervical mucus.

The objectives of this study were to assess whether women who were administered the first injection of the once-a-month contraceptive containing estradiol cypionate and 25 mg depot-medroxyprogesterone acetate (MPA+E(2)C) on Day 7 of their menstrual cycle (delayed injection) exhibit the same degree of cervical mucus changes as women who receive it on Day 5 of their menstrual cycle. This was a multicenter, randomized, controlled clinical trial. A total of 158 women, aged between 18 and 38 years (inclusive), who, were willing to use MPA+E(2)C as their contraceptive method participated in the trial. Participants received a MPA+E(2)C injection on Day 5 (control group, n = 41) or Day 7 (delayed-injection group, n = 117) of their menstrual cycle. Participants who received MPA+E(2)C on Day 5 of their menstrual cycle (control group) exhibited fair or poor mucus quality and poor sperm penetration. Of those women who received MPA+E(2)C on Day 7 of their menstrual cycle (delayed-injection group), 3 (3%) showed good mucus or good sperm penetration at some time point during follow-up. It is possible to conclude that the first injection of MPA+E(2)C given on Day 7 of a menstrual cycle does not provide the same degree of inhibition of mucus quality and sperm penetration as that observed if it is administered on Day 5. However, the theoretical risk of pregnancy after receiving MPA+E(2)C on Day 7 would be expected to be low.

Progestin-only contraceptive rings.

Several progestin-only long acting contraceptives are currently available in the form of implants or injectables. Vaginal rings are another contraceptive option in the final stages of development. These steroid-containing polymer rings are placed in the vagina, providing relatively constant drug release, thus allowing for lower effective doses. Vaginal rings have the advantage of being user-controlled and non-provider dependent, and their use is non-coital related. The first clinical study with medroxyprogesterone acetate vaginal rings was published in 1970. Since then numerous clinical trials testing different steroids and doses have followed. A large Phase III multicenter clinical trial with a levonorgestrel ring, releasing 20 microg/day, was coordinated and sponsored by WHO. The cumulative one-year pregnancy rate was 4. 5%. The principal reasons for discontinuation were menstrual disturbances (17.2%), followed by frequent expulsion of the ring (7. 1%), and vaginal symptoms (6.0%). The finding of erythematous lesions in the vagina in some women has led to the development of a more flexible device. Collaboration with industry should facilitate the manufacture of a redesigned levonorgestrel ring with a higher release rate. The Population Council is also developing a vaginal ring containing Nestorone for 6 months of continuous use. Ovulation inhibition was achieved in over 97% of the segments studied, with rings releasing either 50, 75, or 100 microg/day. No pregnancies occurred in women using the low-dose ring, while one pregnancy each occurred in the intermediate- and high-dose ring groups for a 6-month cumulative pregnancy rate of 0.0, 1.9, and 2.1%. Bleeding irregularities were common. Nestorone is orally inactive; therefore this ring is also excellent for use in lactating women.

Prevalence of enlarged ovarian follicles among users of levonorgestrel subdermal contraceptive implants (Norplant).

OBJECTIVE: The aim of this study was to determine the prevalence of enlarged follicles, as detected by a single clinical or ultrasonographic examination, among users of levonorgestrel subdermal contraceptive implants (Norplant implants). STUDY DESIGN: This was a cross-sectional study of 103 users of Norplant implants and 50 users of the TCu380A intrauterine contraceptive device, all of whom received reproductive health services from PROFAMILIA, Santo Domingo, Dominican Republic. Bimanual pelvic examination and vaginal ultrasonography were performed. Enlarged follicles (>25 mm) were followed up weekly. The chi(2) test was applied to these data. RESULTS: Enlarged follicles were detected by ultrasonography in 17. 5% of Norplant implants users and 4% of TCu380A intrauterine contraceptive device users, respectively (P <.04). There was no difference according to duration of use. The longest time to involution of the follicles was 4 weeks. Forty percent of the enlarged follicles detected by ultrasonography were also detected by bimanual pelvic examination. CONCLUSION: Enlarged follicles are a frequent finding among women who use Norplant implants, but they are less frequent than described in previous studies, which were based on serial ultrasonographic scans in selected groups of users. Physicians and users should be aware of the transient nature of these enlarged follicles, which do not require intervention.

Estradiol-delivering vaginal rings for hormone replacement therapy.

OBJECTIVES: This study was undertaken to determine the relief of climacteric symptoms by vaginal rings delivering estradiol and to monitor estrogen levels. STUDY DESIGN: Rings releasing in vitro either 60 or 140 microg/d estradiol were used by 35 women who had undergone hysterectomy for each dose level. Hot flash and night sweat incidences, vaginal conditions, and complaints were recorded at clinic visits pretreatment and at 1 week, 2 weeks, 1 month, and monthly thereafter through 6 months. Serum samples were assayed for estradiol, estrone, and estrone sulfate. RESULTS: Hot flash incidence was reduced by about 80% with either ring. Vaginal conditions and mood were improved. Fourteen of 70 women discontinued ring use during the trial, 5 because of ring expulsions. Mean (+/-SD) estradiol levels were 123 +/- 48 and 307 +/- 93 pmol/L for the low and high dosage levels, respectively. Mean estrone levels exceeded estradiol levels by 1.7-fold for the higher dosage ring and 2.6-fold for the lower dosage ring. Increases in estrone sulfate concentrations were many times greater than those of estradiol or estrone. CONCLUSIONS: Vaginal rings are an acceptable method of delivery for periods of >/=6 months of doses of estradiol that reduce vasomotor symptoms and improve vaginal conditions. There was little difference in these responses between the 2 dosage levels.

Estradiol delivery by vaginal rings: potential for hormone replacement therapy.

OBJECTIVES: To determine if delivery of estradiol from elastomeric vaginal rings gives estradiol blood levels in the range associated with effective estrogen replacement therapy and to determine the relation between in vitro estradiol release from the rings and blood levels in vivo. Secondary objectives related to changes in lipoprotein cholesterol, changes in climacteric symptoms, and evaluation of acceptability to users. METHODS: Three ring variants releasing approximately 100, 150 and 200 micrograms/day of estradiol in vitro were used through 22 days in 21 postmenopausal women, 7 on each dose levels. Blood samples for measurement of estradiol were taken at 3-4 day intervals. Lipoprotein cholesterol was measured before and at the end of treatment. Women were questioned about climacteric symptoms and about their satisfaction with the ring. RESULTS: Mean serum estradiol levels for the three groups of rings were 63 +/- 6, 94 +/- 5 and 136 +/- 13 pg/ml for the 100, 150 and 200 micrograms/day rings, respectively. FSH levels declined during ring use and the maturation values of cells collected on vaginal swabs markedly increased. Total and LDL cholesterol were significantly reduced and HDL cholesterol was not significantly changed. All women reported relief of postmenopausal symptoms. Vaginal discomfort during the first 3 days of use was reported by 12 women but overall satisfaction with the method was high. CONCLUSIONS: Women using the vaginal rings attained estradiol blood levels compatible with control of climacteric symptoms and bone loss. The relation between in vitro estradiol release and blood levels in vivo was essentially identical for all 3 doses. The use of vaginal rings to deliver estradiol for hormone replacement therapy is judged to merit further evaluation.

Hormonal treatment for bleeding irregularities in Norplant implant users.

OBJECTIVE: Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication. STUDY DESIGN: One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed. RESULTS: Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001). CONCLUSION: The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites.

PIP: In the Dominican Republic, clinical researchers randomly assigned 150 users of the contraceptive implant Norplant who came to Profamilia's Family Planning Clinic in Santo Domingo complaining of bleeding irregularities to one of three treatment groups. They aimed to evaluate the effectiveness of a combined oral contraceptive (OC) with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol (EE) and of 50 mcg EE alone in treating bleeding irregularities. Bleeding irregularities were defined as prolonged bleeding (i.e., 8 or more continuous days of bleeding or spotting) or irregular bleeding (i.e., current bleeding episode initiated after a bleeding-free interval of less than 15 days). Age, parity, duration of Norplant use, and length of bleeding episode before treatment were similar in all three groups (i.e., OC, EE, and placebo). The OC group was significantly more likely to experience ceased bleeding within three days than the two other groups (91% vs. 67% for EE group [p 0.01 from OC group] and 15% for placebo group [p 0.0005 from both treatments]). Bleeding lasting for at least one week occurred less often in the OC group than the two other groups (2% vs. 14% for EE group and 50% for placebo group [p 0.0005 for both treatments]). Duration of bleeding was significantly lower in the OC group than the other two groups (2.6 days vs. 5.4 days for EE group and 12.3 days for placebo group; p 0.0001). Even though women in both hormonal treatment groups were more likely to experience gastralgia or nausea than the placebo group (33-40% vs. 4%; p 0.005), the side effects rarely interrupted treatment. These findings suggested that the OC is a very good effective treatment for bleeding irregularities and is a practical treatment since it is available at all Profamilia clinic sites.

Recent experience with and future directions of contraceptive implants and injectable contraceptives.

Subdermal implantable contraception has been the most important addition to contraceptive technology in the past 2 decades. The Norplant system is only the first of a new family of long acting methods of high effectiveness, high acceptability, and prompt reversibility. The main advantage of the second generation implant systems, to be available soon, is the reduction in the number of implants, which greatly facilitates insertion and removal. However, great improvement in bleeding control is not to be expected. Large and carefully designed epidemiological studies have contributed to clear the main objections to the US Food and Drug Administration (FDA) approval of depot medroxyprogesterone acetate (DMPA) as an injectable contraceptive. New progestin-only, long acting injectables are being tested, but significant improvements over existing methods are difficult to foresee, although every alternative is welcome. Monthly combined injectables have been in great demand, at least in China and Latin America, because of better bleeding control. Improved combined monthly injectables, less estrogenic and more progestin dominated, have been developed and are being introduced in several countries and should soon replace the old monthly injectables. Contraceptive implants and injectables have shown to be an important addition to the contraceptive options available to women throughout both the developing and developed world.

Free levonorgestrel index and its relationship with luteal activity during long-term use of Norplant implants.

Levonorgestrel serum levels and sex hormone binding globulin (SHBG) were measured in 82 women during different years of use of Norplant implants. The ratio between levonorgestrel and SHBG was calculated as an indicator of the free biologically active fraction of levonorgestrel (free levonorgestrel index, FLI). These parameters were then correlated with the presence of luteal activity, as determined by progesterone levels above 9.6 nmol/L, in a sampling run of 10 samples taken twice a week for five consecutive weeks. Levonorgestrel serum levels remained constant around 1.0 nmol/L during the five-year period. SHBG levels were below normal for the first 18 months of use, returning to normal levels during the last three years of use. The FLI in the first two years was significantly higher than that observed in the later years. The frequency of cycles with luteal activity was 12% during the first 2 years, increasing to 44% in the latter years, when FLI levels were lower. Our results suggest that the changes in SHBG and consequently in the free biologically active fraction of levonorgestrel may largely account for the differences in degree of ovarian suppression observed between the first two years of use of Norplant implants and the latter three, even in the absence of a significant variation in total levonorgestrel concentrations.

Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles.

Four different models of contraceptive vaginal rings were tested during three cycles for luteal activity, bleeding control, plasma lipoproteins and serum levels of the contraceptive steroids. Two progestins, levonorgestrel acetate (LNGA) and ST 1435, alone or in combination with ethynyl-estradiol (EE) were tested. The rings released 100 ug/day of the progestins and 30 ug/day of EE. Luteal activity was detected among users of the progestin-only rings: 4 of 8 cycles with ST 1435 and 2 of 10 with LNGA. Only one of the 18 cycles studied with the two combined rings showed luteal activity, but the measurement of contraceptive steroid in plasma suggested that this subject delayed reinsertion of the ring for about one week in that particular cycle. Breakthrough bleeding was observed in 12 of 30 cycles of use of the progestin-only rings, and in only 2 of 27 cycles with the combined models. No significant changes in total cholesterol or its HDL-fraction were observed. However, the only reduction observed in HDL-cholesterol was among users of the LNGA-only ring. It is concluded that the two combined CVR models offer good possibilities of high effectiveness and bleeding control and merit further development.

PIP: Researchers analyzed data on 20 18-38 year old volunteers from the family planning clinic of PROFAMILIA in Santo Domingo, Dominican Republic, who had earlier undergone female sterilization to evaluate 4 different models of contraceptive vaginal rings during 3 cycles so as to identify which models would be the most likely to be an acceptable, safe, and effective family planning method. Women who used either of the 2 combined rings (ethinyl estradiol [EE] and either levonorgestrel acetate [LNGA] or ST 1435) had higher mean total serum levonorgestrel levels than those using the progestin-only rings (LNGA or ST 1435) (most were significant at .005). Luteal activity which marked ovulation was basically limited to users of the progestin-only rings (50% of cycles with ST 1435 and 20% of LNGA). It occurred in 1 of 18 cycles (5.6%) of users of combined rings (LNGA + EE). It probably occurred because of delayed insertion. The combined rings caused fewer incidents of breakthrough bleeding than did the progestin-only rings (7.4% vs. 40%). Neither the progestin-only nor the combined vaginal rings significantly altered total cholesterol or high density lipoprotein (HDL) levels. Users of the LNGA-only ring did experience an insignificant reduction in HDL, however. Further, triglycerides increased among users of the combined vaginal rings, but the increase was only significant with the LNGA + EE ring (25.4 mg/dl increase; p .05). Moreover, they fell significantly among users of the LNGA only ring (45.5 mg/dl decrease; p .05). The researchers concluded that the 2 combined rings hold the most promise due to good bleeding control and high effectiveness and therefore deserve further development.

Norplant implants: the mechanism of contraceptive action.

OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

PIP: This study sought to determine if fertilization can occur unnoticed among Norplant users who are ovulatory. Serial blood samples were obtained during a 1-month period from women receiving contraceptive service and healthcare at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. These women were all sexually active Norplant users who experienced regular menstrual bleeding patterns, and their sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG) at the Department of Biomedical Sciences at the University of Tampere, Finland. There was also a control group of 20 noncontracepting women included who were trying to conceive. Duration of Norplant was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th, 3 in the 5th year, and 1 in the 7th year. Pregnancy determination was based on the presence of hCG in the luteal phase by use of a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days postovulation. 9 pregnancies were detected, all in the control group who were trying to conceive. 6 of these advanced to clinical pregnancies and 3 terminated spontaneously at the next menstrual period. None of the Norplant users evidenced and hCG production, whether or not the observed cycles were ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1/50 and 1/150,00. The null hypotheses that Norplant users conceive at a natural rate can be rejected at the 0.05 level. Thus, interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.

Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

PIP: The study sought to examine the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. This observational, prospective, case-controlled, comparative study occurred at the Family Planning Clinic of PROFAMILIA in Santo Domingo, Dominican Republic. 31 subjects agreed to receive Norplant contraceptive implants between 13-77 months prior to this study and there were 12 nonhormonal contraceptors who also volunteered to participate. Follicle stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for 1 menstrual cycle, and almost 1/2 of the cycles of norplant acceptors were anovulatory: the remainder (55%) had some form of dysfunction such as diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from controls. Anovulation is clearly 1 of the main mechanisms of Norplant action, but even in presumptive ovulatory cycles, the dysfunctions described could have contributed to the high contraceptive effectiveness of Norplant.

IUDs and PID: a comparative trial of strings versus stringless devices.

An international multicentered clinical trial was designed to determine the possible role of intrauterine device (IUD) marker strings in the etiology of pelvic inflammatory disease (PID). A total of 1265 women were admitted and randomly allocated to receive either a standard TCu200 IUD or a TCu200 IUD without marker strings. These patients were followed-up through 12 months postinsertion. No statistically significant differences were found between the two groups of IUD users with respect to the incidence of PID or other types of infection or inflammation. The 12-month life table termination rates and overall continuation rates were also similar for users of the respective devices, with the exception of removal rates for bleeding/pain, which were significantly higher in the strings group than in the stringless group. However, the number of bleeding/pain complaints ever reported during the study were not statistically different in the two study groups. The study results indicate that the IUD string does not play an important role in the etiology of PID associated with the use of IUDs.

Hormonal changes associated with bleeding during low dose progestogen contraception delivered by Norplant subdermal implants.

The main side effect associated with the use of Norplant contraceptive implants is a disruption of the menstrual bleeding pattern. To explore the relationship between bleeding and hormonal changes, we analyzed the estradiol (E2) and progesterone (P) patterns that preceded bleeding episodes or that corresponded to periods of amenorrhea in 103 cycles observed among 82 women using Norplant subdermal implants. Five different bleeding patterns were defined: 'normal' (24-45 day cycles), oligomenorrhea (46-90 day cycles), amenorrhea (over 90 day cycles), irregular/frequent bleeding (less than 25 day cycles), and prolonged bleeding (continuous bleeding/spotting for more than 10 days). All 'normal' cycles were associated with a rise followed by a fall in E2 levels preceding bleeding. In half of the 'normal' cycles (28/54), a rise and fall of P was also observed. The same pattern was found in oligomenorrheic cycles, but only two of 12 cycles had a rise and fall of both E2 and P. None of the subjects with amenorrhea had luteal activity. Six of the nine amenorrheic cycles displayed persistently low E2 levels (below 75 pg/ml). The remaining three had a moderate elevation in E2 levels during the sampling period. Sixty percent of the subjects who showed irregular/frequent bleeding (15/25) had low E2 levels (less than 75 pg/ml), without luteal activity, and bleeding occurred without clear evidence of a further drop in E2 levels. In the remaining 40%, bleeding was preceded by a rise and drop of E2 without luteal activity, with the exception of one women, who exhibited a rise and fall of both E2 and P. Samples were obtained in only three subjects during continuous bleeding. One had low E2 levels, and the remaining two bled continuously, in spite of having E2 levels in the normal range. We conclude that ovarian hormones continue to influence endometrial shedding during the use of Norplant contraceptive implants.

Ovarian endocrine function through five years of continuous treatment with NORPLANT subdermal contraceptive implants.

Ovarian endocrine function was assessed in 88 women using NORPLANT subdermal implants during different periods of use and in a control group of 15 women using non-hormonal contraception. Blood samples for estradiol (E2) and progesterone (P) assays were obtained twice a week for five consecutive weeks. Three distinct E2 patterns were observed: one was characterized by fluctuating levels within a normal range (20 to 400 pg/ml), a second pattern corresponded to continuous low E2 levels (below 75 pg/ml in the 10 samples) and the third was characterized by high broad estradiol peaks reaching over 400 pg/ml. The proportion of sampling runs characterized by normal fluctuating levels increased from 38% in the first two years of use to 80% during the fifth year of use. Low E2 profile was only observed during the first two years of use (27%) and in only 1 case at the beginning of the third year of use (5%). The percentage of cycles with high broad estradiol peaks remained between 20-40% without a clear tendency to change in either direction with duration of use. Thirty-three percent of the observed sampling runs had luteal activity (P above 3 ng/ml). The proportion of runs with luteal activity increased from 14% during the first two years of use to 40% during the third and fourth, and 60% during the fifth year of use. All control subjects had luteal activity. The mean highest progesterone level was lower in the NORPLANT runs (8.7 +/- 3.9 ng/ml) as compared to the controls (11.3 +/- 3.8 ng/ml). NORPLANT sampling runs with luteal activity had normal fluctuating E2 levels with only one exception. However, not all cycles with normal E2 levels showed luteal activity. On the other hand, all runs with low E2 levels or high broad E2 peaks were without luteal activity. In summary, women using continuous low-dose levonorgestrel contraception through NORPLANT subdermal implants, have a variable degree of ovarian activity as compared with the more complete depression of ovarian function observed among pill or injectables' users. Ovarian activity becomes closer to normal during the third through fifth year of use.

PIP: Ovarian endocrine function was assessed in 88 women using NORPLANT subdermal implants during different periods of use and in a control group of 15 women using non-hormonal contraception. Blood samples for estradiol (E) and progesterone (P) assays were obtained twice a week for 5 consecutive weeks. 3 distinct E patterns were observed; one was characterized by fluctuating levels within a normal range (20 to 400 pg/ml), a 2nd pattern corresponded to continuous low E levels (below 75 pg/ml in the 10 samples) and the 3rd was characterized by high broad estradiol peaks reaching over 400 pg/ml. The proportion of sampling runs characterized by normal fluctuating levels increased from 38% in the first 2 years of use to 80% during the 5th year of use. Low E profile was only observed during the first 2 years of use (27%) and in only 1 case at the beginning of the 3rd year of use (5%). The % of cycles with high broad estradiol peaks remained between 20-40% without a clear tendency to change in either direction with duration of use. 33% of the observed sampling runs had luteal activity (p 3 ng/ml). The proportion of runs with luteal activity increased from 14% during the first 2 years of use to 40% during the 3rd and 4th, and 60% during the 5th year of use. All control subjects had luteal activity. The mean highest progesterone level was lower in the NORPLANT runs (8.7 + or - 3.9 ng/ml) as compared to the controls (11.3 + or - 3.8 ng/ml). NORPLANT sampling runs with luteal activity had normal fluctuating E levels with only 1 exception. However, not all cycles with normal E levels showed luteal activity. On the other hand, all runs with low E levels or high broad E peaks were without luteal activity. In summary, women using continuous low-dose levonorgestrel contraception through NORPLANT subdermal implants, have a variable degree of ovarian activity as compared with the more complete depression of ovarian function observed among pill or injectables' users. Ovarian activity becomes closer to normal during the 3rd through 5th year of use. (Author's).

The clinical performance of NORPLANT implants over time: a comparison of two cohorts.

This paper reports on a study that compared the clinical performance of NORPLANT implants in two separate but similar cohorts: 200 NORPLANT users from 1975 through 1978, when the method was first introduced in the clinic, and 212 users in the same population from March 1982 through December 1983. Two different cohorts of Copper T IUD users were included as controls. Continuation rates, at one and two years of use, were significantly higher in the second group of NORPLANT users (88.1 vs. 60.5 and 76.5 vs. 40.8, respectively). Statistically significant differences between the NORPLANT cohorts were observed in discontinuation due to bleeding, amenorrhea, other medical causes, total medical causes, and personal reasons. No differences in clinical performance of the IUD were observed between the two control groups. The higher continuation rate in the second group of implant users is attributed to greater confidence and experience among the clinic staff between 1982 and 1983, and greater knowledge of and familiarity with the method among those in the target population. The study also shows that the first clinical trials of a new contraceptive method may not provide an accurate picture of that method's ultimate performance.

Absence of chorionic gonadotropin in sera of women who use intrauterine devices.

A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the intrauterine contraceptive device (IUD). Starting on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, we collected daily blood samples from three groups of normally menstruating young women. The study groups were (A) IUD users (n = 30), (B) women with tubal ligation (n = 30), and (C) women trying to become pregnant (n = 15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. Two subjects who became pregnant, as judged by progressive increases in hCG and P levels in the luteal phase, belonged to the group planning pregnancy. The finding of two pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

PIP: A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the IUD. Beginning on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, the authors collected daily blood samples from 3 groups of normally menstruating young women. The study groups were: a) IUD users (n=30); b) women with tubal ligation (n=30); and c) women trying to become pregnant (n=15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. 2 subjects who become pregnant as judged by progressive increases in hCG and P levels in the luteal phase belonged to the group planning pregnancy. The finding of 2 pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

Contraception with long-acting subdermal implants. A five-year clinical trial with Silastic covered rod implants containing levonorgestrel. The International Committee for Contraception Research (ICCR) of the Population Council.

A total of 189 women volunteered to accept subdermal implants for contraception. The implants were "covered rods", consisting of a core rod containing equal parts by weight of levonorgestrel and polydimethylsiloxane and sealed inside a thin-walled tube of Silastic tubing with medical adhesive. In one study 78 women used 4 3cm rods (study 07) and in the other 111 women used 6 3cm rods. In 5 years of use there were no pregnancies in either group. Terminations because of menstrual problems were twice as frequent among the 4-rod users than among users of the 6 rods. Menstrual pattern analysis is presented for the two rod regimens and compared with the previously reported patterns for the 6-capsule regimen (NORPLANT). Long--term in vivo release rates are also presented.

Serum prolactin profiles of normal human conceptual cycles.

Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays (RIA) for prolactin (hPRL), estradiol-17 beta and luteinizing hormone (hLH). Two of the observed subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPRL were observed in either subject. Enormous spikes were observed in daily prolactin values, with wide variations between subjects.

PIP: Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays for prolactin (hPRL), estradiol-17beta, and luteinizing hormone (hLH). Two of the subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPRL were observed in either subject. Enormous spikes were observed in daily hPRL values, with wide variations between subjects.