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Biomedical subjects

A S Tejada

Publications and source records attributed to A S Tejada.

13 recordsLinked to original sources

Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study.

BACKGROUND: Levonorgestrel (LNG) consistently prevents follicular rupture only when it is given before the onset of the ovulatory stimulus. As locally synthesized prostaglandin (PG) plays a crucial role in follicular rupture and cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after the ovulatory process had been triggered by the gonadotrophin surge. METHODS: Forty-one women were divided into two groups. One was treated when the size of the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a randomized order. Serial blood sampling for the assay of LH and follicular monitoring by transvaginal ultrasound were performed before and after treatment. RESULTS: Follicular rupture failed to occur within the 5-day period that followed treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P < 0.052). The overall proportion of cycles with no follicular rupture or ovulatory dysfunction increased significantly by the addition of Melox to LNG (66 versus 88%, P < 0.012; n=41-matched pairs). CONCLUSIONS: The trend towards increased incidence of no follicular rupture when Melox was combined with LNG suggests that the addition of a cox-2 inhibitor has the potential to improve the contraceptive efficacy of LNG by a pre-fertilization effect.

Adolescent↗

Correlation of endocrine profiles with bleeding patterns during use of Nestorone contraceptive implants.

The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (</= 24 days), 36 normal (25-35 days), 27 long (36-90 days) and nine episodes of amenorrhoea, as well as 28 periods of prolonged bleeding, were identified. Short cycles, periods of prolonged bleeding and amenorrhoea were characterized by low oestradiol concentrations. Bleeding after a normal or long cycle regularly occurred after a rise and fall of oestradiol or oestradiol and progesterone. The duration of bleeding was directly and significantly associated with the highest concentration of oestradiol in the previous 15 days in anovulatory cycles. Luteal activity was associated with shorter duration of bleeding. Periods of prolonged bleeding were usually initiated with a drop in oestradiol and over half ended with an increase in oestradiol. It was concluded that changes in endogenous hormone have a significant influence over the bleeding pattern during use of NES implants.

Adolescent↗

Sex hormone binding globulin and free levonorgestrel index in the first week after insertion of Norplant implants.

Levonorgestrel has an inhibitory effect on sex hormone binding globulin (SHBG). This decrease in SHBG leads to an increase in the free levonorgestrel index (FLI), which has a stronger biological effect. The interaction between serum levels of levonorgestrel and SHBG in long-term users of Norplant implants has been described. This study was designed to understand the same interaction immediately after the insertion of the implants, in a group of 16 women, sampled at 0 and 6 h and at 1, 3, and 7 days after Norplant implant insertion. Peak serum levonorgestrel levels were achieved at 24 h after insertion, remaining stable on day 3 and decreasing by > 10% by day 7. SHBG did not change during the first 24 h, but decreased by 19% and 60% on days 3 and 7, respectively. FLI more than doubled from day 1 to day 7 after insertion. The large decrease in SHBG and doubling of FLI is not followed by a similar reduction in levonorgestrel, which is hard to explain without an increase in the release rate of the steroid from the capsule.

Contraceptive Agents, Female↗

Ultrasonographic and endocrine evaluation of ovarian function among Norplant implants users with regular menses.

With the objective of evaluating the ovulatory function among long-term Norplant implants users with regular menstrual cycles, we undertook this prospective study including 11 Norplant implants users and 11 control women who were not using hormonal methods of fertility control. Exposed and unexposed women had had at least three regular menstrual cycles preceding enrollment. All women were followed during one menstrual cycle by serial vaginal ultrasound and estradiol (E2), progesterone (P), LH, and FSH measurements. Three Norplant implants users ovulated, three had luteinization of an unruptured follicle (LUF), three had persistent follicle growth up to a mean of 33 mm without rupture, and two had no follicular development beyond 16 mm. Ten of the controls had normal ovulation and one had LUF. Mean peak LH and FSH among Norplant implants users who ovulated were three- to four-fold lower than among controls. Although users of Norplant implants with regular cycles frequently have luteal activity, the results of this study suggest that elevation of P during the second half of the cycle does not necessarily indicate ovulation has occurred and may frequently be associated with the presence of luteinized unruptured follicle. When ovulation occurs, there are usually abnormal hormone levels (low LH/FSH peak, low progesterone) which may also contribute to the contraceptive effect of Norplant implants.

Contraceptive Agents, Female↗

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.

Drug Implants↗

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.

Amenorrhea↗

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.

Adult↗

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.

Contraceptive Agents, Female↗

Prospective study of the pituitary-ovarian function after tubal sterilization by the Pomeroy or Uchida techniques.

Surgical sterilization has become one of the most widely used methods of fertility regulation in the world. A common concern is the not yet clarified possible disturbance of the ovarian function resulting from the surgical procedure. A prospective study was carried out to contribute toward answering this question. Twenty subjects were enrolled in a longitudinal study of ovarian endocrine function before, and 2 and 6 months after, tubal ligation. The Pomeroy technique, which may compromise ovarian circulation, and the Uchida technique, which is free of this risk, were used randomly. Eight women who underwent to the Pomeroy technique and 9 who underwent the Uchida technique completed the protocol. Luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone were measured daily from days 10 through 18 of the cycle and every other day until the onset of the next menses. No change in any of the hormones studied was observed, with the exception of a significant increase in progesterone 2 months after tubal ligation by the Uchida technique.

Female↗

The role of the levonorgestrel intrauterine device in the prevention and treatment of iron deficiency anemia during fertility regulation.

Hematocrit and blood ferritin were assayed in 43 women using a levonorgestrel intrauterine device (LevoNg-IUD), 49 using the Copper T-380 Ag (T-Cu 380 Ag), 27 using the Lippes loop and 30 non-IUD users as controls. The mean duration of use was 41 months for the three IUD groups. Women not using IUDs and with similar age, parity, years of schooling and family income as users had a normal mean hematocrit and ferritin, but 30% had low hematocrit (below 38%) and 43% had low ferritin (below 11 ng/ml). After prolonged use of the IUDs, 26% of users of Lippes loop, 22% of users of T-Cu 380 Ag and only 2% of users of LevoNg-IUD had subnormal hematocrit; 70%, 55% and 14%, respectively, had low ferritin. Thus, in a population with high incidence of anemia, the use of LevoNg-IUD appears to reduce the proportion of women with clinical anemia and with depletion of their iron store.

Adult↗

Subjective perception of bleeding and serum ferritin concentration in long-term users of Norplant.

UNLABELLED: Serum ferritin was measured in 4 groups of long-term users of NORPLANT implants. The users were divided according to their own subjective perception of bleeding: a random sample of 46 one year active users; 30 active users who had increased bleeding; 39 women who had increased bleeding and had the implants removed; 28 active or terminated users who had reduced bleeding. These four groups were compared with a control group of 68 new acceptors of any method at the same clinic who met the criteria for use of NORPLANT. The mean age, parity, years of schooling and family income were similar for the 5 groups. Mean hematocrit for all NORPLANT groups were significantly higher than the control group. About half of the NORPLANT subjects and controls with normal hematocrit had ferritin levels below 11 ng/ml. The proportion of subjects with ferritin less than 11.0 ng/ml were: Group 1) 48%; 2) 63%; 3) 77%; 4) 36% and CONTROLS: 57%. Mean iron stores for all NORPLANT users did not differ significantly from those of a demographically similar control group. Significant differences were, however, observed in two subgroups of NORPLANT users. Those women who had increased bleeding and requested implant removal had lower mean ferritin levels and those who perceived decreased bleeding as a result of NORPLANT use had higher ferritin concentration.

Adult↗

Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device.

Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly.

Adult↗

Abnormal endocrine profile among women with confirmed or presumed ovulation during long-term Norplant use.

FSH, LH, estradiol and progesterone were serially assayed during 8 cycles of six subjects using six subdermal implants releasing levonorgestrel (NORPLANT) for a period of 2 to 6 years. All 8 cycles studied had a very low LH peak and a low or nonexistent FSH peak as compared to 8 control cycles. The mean LH peak for NORPLANT users was 33.9 mIU/ml as compared to 142 mIU/ml in the control group; and FSH was 13.0 mIU/ml as compared to 31.3 mIU/ml in controls. A subsequent rise in progesterone was observed in the 8 cycles studied, but the mean mid-luteal levels were significantly lower than in controls (9.0 ng/ml vs. 15.6 ng/ml). No differences were observed in the estradiol curve. Two of the subjects using NORPLANT had a laparotomy performed on days 17 and 20 of the cycle, for surgical sterilization purposes. A distinctive corpus luteum with a stigma was observed. Our results indicate that women under prolonged use of NORPLANT do not have normal endocrine cycles, even though they may ovulate. It is doubtful however, that these ovulatory cycles can be fertile under the abnormal endocrine conditions found in our subjects. In addition to the possible effect of luteal insufficiency, the normal maturation of the oocyte may be impaired.

Adult↗