Biomedical subjects

M Pavez

Publications and source records attributed to M Pavez.

At least 19 recordsLinked to original sources

PubMed2004

Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation.

We assessed to what extent the standard dose of levonorgestrel (LNG), used for emergency contraception, or a single dose (half dose), given in the follicular phase, affects the ovulatory process during the ensuing 5-day period. Fifty-eight women were divided into three groups according to timing of treatment. Each woman contributed with three treatment cycles separated by resting cycles. All received placebo in one cycle, and standard or single dose in two other cycles, in a randomized order. The diameter of the dominant follicle determined the time of treatment. Each woman had the same diameter assigned for all her treatments. Diameters were grouped into 33 categories: 12-14, 15-17 or 18-20 mm. Follicular rupture failed to occur during the 5-day period in 44%, 50% and 36% of cycles with the standard, half dose and placebo, respectively. Ovulatory dysfunction, characterized by follicular rupture associated with absent, blunted or mistimed gonadotropin surge, occurred in 35%, 36% and 5% of standard, single dose or placebo cycles, respectively. In conclusion, LNG can disrupt the ovulatory process in 93% of cycles treated when the diameter of the dominant follicle is between 12 and 17 mm. It is highly probable that this mode of action fully accounts for the contraceptive efficacy as well as the failure rate of this method. The present data suggest that half the dose may be as effective as the standard dose.

Adolescent↗

PubMed2001

Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants.

Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study of 199 users of Jadelle rod implants. We examined drug levels, patterns of changes, factors affecting drug levels, and concentrations at which pregnancies occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of the third and fifth years neither mean nor median serum levels varied markedly. At 5 years the mean concentration was again 64% of the first month's mean. Declining levels were observed thereafter through the end of 7 years when the mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations of women who became pregnant during Jadelle use had mean and median values of 152 and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated ponderal index, body weight, duration of use, and a single clinical center were the most important variables affecting measured levonorgestrel levels. Approximately one-third of assays in the sixth and seventh years were found to be below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not maintain sufficiently high levels of effectiveness against pregnancy after 5 years and that heavier women would then be at greater risk of pregnancy.

Adolescent↗

PubMed2000

Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study.

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.

Adolescent↗

PubMed1998

The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study.

A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.

Adult↗

PubMed1997

Clinical performance of a new two-rod levonorgestrel contraceptive implant: a three-year randomized study with Norplant implants as controls.

In a randomized three-year clinical trial at seven clinics, the performance of levonorgestrel rod (LNG ROD) implants used by 600 women was compared with that of soft tubing NORPLANT implants used by 598 women. No pregnancies occurred in either group of women and, accordingly, body weight did not affect the efficacy of either type of implant. There were neither statistically significant nor important differences in termination rates for any reason over the three years. Complaint and illness rates during use of either of the two implant types were statistically indistinguishable and were attributable to the same set of conditions. Seventy-one per 100 of the women using each implant regimen continued to the three-year point, for an average annual continuation rate of 89 per 100. Removals of LNG ROD implants were accomplished in about half the time required for removal of Norplant capsule implants (p < 0.001).

Adolescent↗

PubMed1997

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Adolescent↗

PubMed1997

First week drug concentrations in women with levonorgestrel rod or Norplant capsule implants.

Forty-two healthy women volunteered to have blood samples drawn at 2, 4, 8, 24, 48, and 168 h (7 days) following placement of levonorgestrel-releasing rod (LNG rod) or of Norplant capsule implants to permit measurement of drug concentrations. Three clinics recruited 10 women each, half of whom used each type of implant. Twelve additional subjects were later enrolled at one site to provide greater detail for the capsule implants. Throughout the week, women with Norplant implants had apparently higher mean drug concentrations than did women with LNG rod implants, but the differences were significant only in the first 48 h after placement (p < 0.05). Maximum levels for capsule implants were found at the 24-h sample (mean, 1358 to 1474 pg/mL) and for the LNG rod implants at 48 h (772 pg/mL). Body weight was negatively correlated with levonorgestrel concentrations at all times (p < 0.05). For several sampling times, differences between clinics in mean concentrations were statistically significant after weight adjustment. Despite differences by implant type, weight, or clinic location, drug concentrations compatible with contraceptive effect were attained within 24 h in users of LNG rod or of Norplant implants, insofar as all women had levonorgestrel concentrations above 250 pg/mL at the 24-h sample.

Adolescent↗

PubMed1995

Clinical trial with Nestorone subdermal contraceptive implants.

The clinical performance and the in vivo release rate of a single 4-cm Nestorone subdermal implant were investigated. Implants manufactured by two different procedures were compared. Volunteers were 70 healthy women of proven fertility. Forty women provided blood samples twice a week in the pretreatment cycle and for 5-6 weeks at 6-month intervals during treatment. Additional control cycles (n = 31) were studied in 19 Copper T users. No pregnancy occurred in 1570 woman-months. Nestorone plasma levels (x +/- S.E.) declined from 112 +/- 8 to 86 +/- 3 pmol/L (Implant A) and from 145 +/- 8 to 57 +/- 5 pmol/L (Implant B) from the first to the 24th month. Progesterone levels were < 9.5 nmol/L in 166 (93%) of 178 blood samplings taken during treatment. Progesterone levels > 16 nmol/L were found in only 7 sampling periods (3.9%) in treated women and in 70 (98.6%) out of 71 control cycles. No ovulation occurred with Nestorone plasma levels above 105 pmol/L. No abnormal changes were observed in plasma lipoproteins or other clinical chemistry parameters during treatment. The implants were well tolerated. The most frequent complaint was the occurrence of irregular bleeding. Enlarged follicles found during pelvic examination in 8 subjects (11.4%) disappeared spontaneously in 10 days to 6 weeks. Implants were removed because of medical (n = 10, 14.3%) or personal reasons (n = 6, 8.6%) or at the 24th month of treatment (n = 54, 77.1%). The estimated average daily in vivo release rate of Nestorone was 45-50 micrograms/day. A single Nestorone subdermal implant affords efficient contraceptive protection during two years.

Adolescent↗

PubMed1993

Four-year experience in a randomized study of the Gyne T 380 Slimline and the Standard Gyne T 380 intrauterine copper devices.

Performance of the Slimline and Standard models of the Gyne T 380 were measured through four years in a comparative study initially involving 996 women, seventy percent of whom were randomized to the Slimline device. Cumulative pregnancy rates of Slimline users were 0.3 +/- 0.2 per 100 both at three and at four years, as compared with rates of 1.5 +/- 0.9 and 3.8 +/- 1.7 at the same intervals for users of the Standard model (P > .05). The four-year explusion rate of the Slimline, 8.6 +/- 1.3 per 100, was significantly higher than the comparable rate of the Standard model, 4.4 +/- 1.6 (P < .05). The two Gyne T* models did not differ in continuation rates. First time IUD users, however, had substantially lower continuation rates than did former users (P < .001), in consequence of their relative youth and desire to have additional children. Other performance measures did not differ importantly by device.

Adolescent↗

PubMed1992

Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users.

This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L-Ng), estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE2) daily for 10 days in 10 volunteer women using NORPLANT implants. Six of these volunteers were also treated with 20 ug of EE2 daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE2 daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE2 pill. In contrast, the levels of E2 and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT implants is constant, it follows that the effect of EE2 on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG. It is concluded that in NORPLANT users, SHBG and L-Ng, but not the endogenous ligands, behave in a predictable manner in response to EE2. Thus, this model affords the possibility of exploring the influence of SHBG on tissue response to progestins.

Dihydrotestosterone↗

PubMed1991

Clinical trial with 3-keto-desogestrel subdermal implants.

The study was done to assess the clinical performance and in vivo steroid release rate of 3-keto-desogestrel subdermal implants designed to deliver 5 different doses of the progestin. Volunteers were healthy women of proven fertility who provided blood samples at scheduled intervals during treatment. No pregnancy occurred in 514 woman-months in users of implants delivering 30 and 40 micrograms per day of 3-keto-desogestrel. Three pregnancies, one ectopic, were observed in 109 woman-months recorded with implants delivering 20 micrograms per day or less. Ovulation was inhibited, as judged by depressed progesterone levels, in 57 of 59 (97%) blood samplings in women whose 3-keto-desogestrel plasma levels were greater than 0.28 nmol/L and in 39 of 75 (52%) of cases with lower levels. Users of 4 cm implants manufactured by The Population Council, New York, showed mean levels above 0.28 nmol/L until 18 months of use. Levels achieved with 4.4 cm implants manufactured by Organon, Oss, Holland, were less consistent. No changes were observed in the plasma lipoprotein pattern or clinical chemistry during treatment. The main complaint was the occurrence of bleeding irregularities, particularly with the lower doses. Ovarian cysts found during pelvic examination in 11 (22%) subjects disappeared spontaneously within 7-90 days. 3-keto-desogestrel implants releasing around 40 ug/day and providing plasma levels around 0.28 nmol/L afford efficient contraceptive protection.

Adolescent↗

PubMed1991

Prolonged intrauterine contraception: a seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDS.

A levonorgestrel-releasing IUD and the Copper T 380Ag IUD were in randomized comparison for seven years in five clinics. In two other clinics the randomized study was truncated at five years, but use of the Copper T continued. No pregnancies occurred to users of either device in years 6 and 7. Cumulative pregnancy rates were 1.1 per 100 at seven years for the steroid-releasing and 1.4 per 100 for the copper-releasing IUDs. Cumulative rates of PID did not differ between devices. Infection rates appeared to be lowest during the sixth and seventh years of the study. Termination attributable to amenorrhea was the principal contributor to differences in cumulative continuation rates between devices. At the five clinics that carried the comparative study to seven years, cumulative continuation rates were 24.9 per 100 for LNg20 IUD users and 29.4 per 100 for TCu 380Ag users. Women who used either method for periods of five to seven years experienced, on average, marked to mild increases in hemoglobin as compared with levels at admission. The Copper T380 family and the LNg20 IUDs represent the most effective reversible contraceptive methods yet studied in long-term randomized trials.

Adolescent↗

PubMed1991

Two-year comparative trial of the Gyne T* 380 Slimline and Gyne T* 380 intrauterine copper devices.

In a randomized trial of the Gyne T* 380 Slimline, the-two year pregnancy rate was 0.3 per 100 and the continuation rate was 65 per 100. These rates did not differ statistically from those of the standard Gyne T* 380, nor did other performance parameters differ between devices by the log-rank test. Women under age 30 had lower continuation rates using either device than did women age 30 or older at admission because of removals for planned pregnancy. Conception rates among those who desired pregnancy were 35 per 100 at one month and 86 per 100 at one year.

Adult↗

PubMed1990

A randomized trial of the Gyne T 380 and Gyne T 380 Slimline Intrauterine Copper devices.

To facilitate manufacture and insertion of the Gyne T 380 IUD, design changes were instituted. Copper collars were seated flush at the ends of the horizontal crossbar of the device. A randomized study of the Gyne T 380 Slimline, the new design, was undertaken in comparison with the standard Gyne T 380. A total of 996 women were enrolled, with 698 Slimline insertions and 298 of the standard Gyne T. No statistically significant difference in ease of insertion or in performance was detected between the models. At one year, the pregnancy rate of each model was below 0.5 per 100 and the continuation rate was 79-80 per 100. Pelvic inflammatory disease or endometritis was found in one percent of subjects in the first year. This is the seventh multicenter randomized study of a collared T IUD with 380 mm2 of copper surface. In all seven, the one-year gross pregnancy rate has been 1.2 per 100 or lower.

Adult↗

PubMed1990

Clinical assessment of treatments for prolonged bleeding in users of Norplant implants.

The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use.

Administration, Oral↗

PubMed1989

A longitudinal study on cortisol, prolactin and thyroid hormones in users of Norplant subdermal implants or a copper T device.

A longitudinal study was undertaken to assess PRL, cortisol, TSH, T3 and T4 levels in NORPLANT implant users (n = 22) and Copper T users (n = 20). Participants were healthy women with no contraindication for hormonal contraception. Samples were drawn at 0930 to 1000 h twice pretreatment and at month 2, 4, 6, 12, 24 and 36 after insertion. At the second treatment month, a second sample was obtained at 1600 h to assess cortisol diurnal variation. Hormones were measured by RIA. Values for all hormones were similar in Norplant and Copper T users. No significant changes occurred throughout the study period. Elevated PRL levels (greater than 500 mU/1) were found in three women from each group before and during treatment but no clinical evidence of hyperprolactinemia was detected. The results of this study reassure that long-term use of NORPLANT implants do not impair plasma levels of cortisol, prolactin and thyroid hormones.

Adult↗

PubMed1989

[Long-term follow-up of women treated with contraceptive implants of levonorgestrel Norplant].

This report describe the long-term follow-up of 376 women who received Norplant implants in the period october 1974 through may 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set. The average levonorgestrel plasma levels declined steadily through eight years of use of Norplant capsules (r = -937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area. The levonorgestrel half-life after implant removal was 42 +/- 16 h (X +/- S.E.) and only trace amounts are detected after 96 h. Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first years of Norplant implants use was 0.63. No pregnancy has occurred in 5.020 woman-months observed during treatment with a second set of capsules. Fifty-six women (14.9%) out of 376 acceptors of the first implant and 12 (10.9%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly side effects commonly associated with hormonal contraception. Removals for bleeding problems occurred in 5.6% and 3.6% of the acceptors of the first and second implant, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Estradiol plasma levels during long-term treatment with Norplant subdermal implants.

Estradiol-(E2) plasma levels were assessed in forty-seven women treated for one through seven years with the same set of Norplant implants. Each woman was subjected to one (n = 34), two (n = 11) or three (n = 2) sampling runs. At each sampling run, blood samples were drawn every third or fourth day during 5 or 6 consecutive weeks. Sampling runs were classified as ovulatory (n = 11), anovulatory (n = 49) or uncertain (n = 1) according to progesterone levels. Controls were Copper T users (n = 8), all classified as ovulatory. No significant differences were found for the mean E2 levels between Norplant users and Copper T users and between ovulatory and anovulatory cases. The mean of the peak E2 value found in each sampling run was significantly higher in anovulatory Norplant subjects than in the control group. The mean of the minimum E2 level observed was significantly lower in Norplant cases than in Copper T users. A single woman from the Norplant group and none from the Copper T group had all E2 values below 370 pmol/l. The inhibition of the reproductive function induced by Norplant implants is associated with a wider range of E2 circulating levels. None of the values observed at the extremes should cause serious concerns. High peaks are transitory and opposed by the antiestrogenic effect of levonorgestrel. Persistent low levels which could be associated with a hypoestrogenic state were observed in a single case.

Adult↗