Biomedical subjects

V Brache

Publications and source records attributed to V Brache.

At least 37 records · Page 2Linked to original sources

PubMed1999

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↗

PubMed1999

Variations in vaginal epithelial surface appearance determined by colposcopic inspection in healthy, sexually active women.

A total of 107 sexually active women, aged 18-35 years, was recruited through family planning clinics in four centres in different countries. Each woman underwent two or three gentle but thorough and systematic vaginal inspections using a consistent technique with colposcopic magnification over a 4-6 month period to look for changes in vaginal and cervical appearance which might be related to sexual intercourse, tampon use, contraceptive method used, cigarette smoking or other environmental factors. Obvious changes in appearance were photographed at x10 magnification. These 'appearances' or 'conditions' were classified according to a modification of the recommendations of a workshop sponsored by the World Health Organization, the Population Council and the Conrad Program. Most of these alterations in the appearance of the vaginal epithelium were judged to be of such minor clinical importance that they have been termed 'conditions' or 'changes in appearance' rather than 'lesions'. In all, 56 'conditions' or 'appearances' were noted in 314 inspections, the commonest being petechiae (53.6%). Potentially significant conditions justifying the term 'lesions' (three microulcerations, two ecchymoses, five abrasions and one mucosal tear; 3.5% of inspections) usually healed spontaneously and disappeared rapidly. The incidence of these conditions was highest when the inspections followed intercourse in the previous 24 h (25.2 versus 14.2%; P < 0.0008), or tampon use (32.4 versus 15.9%; P < 0. 0001). These processes may be regarded as a reflection of regular minor trauma to the vaginal epithelium.

Adolescent↗

PubMed1998

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

Contraceptive Agents, Female↗

PubMed1998

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↗

PubMed1998

Contraception with two levonorgestrel rod implants. A 5-year study in the United States and Dominican Republic.

A 5-year trial of a two-rod contraceptive implant, which releases the progestin levonorgestrel (LNG rod), was conducted at four clinics with 594 women. Mean age and weight at admission were 25.5 years and 62.4 kg, respectively. Consent to continue through 5 years was sought and obtained when the 3-year cumulative pregnancy rate proved to be 0.8 per 100. No pregnancies occurred in the fourth or fifth years. The 5-year cumulative pregnancy rate was, therefore, 0.8 per 100 with an annual average pregnancy rate below 2 per 1000 women. Prolonged bleeding/spotting (8.2% of subjects) and irregular bleeding (5.6%) were the most frequently cited medical reasons for removal. Removals for headache (4.7%) and weight change (4.0%) were the next most frequent medical reasons. Between 1% and 2% of subjects during the 5-year trial sought removals for each of the following conditions: mood changes, lower abdominal pain, depression, or pain at the implant site. The mean annual continuation rate during the study was 77 per 100. Use per woman averaged 2.96 years. Mean removal time was 5.9 +/- 0.6 min. These data indicate that, for a 5-year period, the two LNG rod implants are equivalent to the six Norplant capsule implants with respect to safety and efficacy parameters, but permit easier and more rapid implant removal.

Adolescent↗

PubMed1998

Timing of onset of contraceptive effectiveness in Norplant implant users. Part I. Changes in cervical mucus.

OBJECTIVE: To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinics. PATIENT(S): Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study. INTERVENTION(S): Cervical mucus and blood samples were obtained. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel. RESULT(S): The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration. CONCLUSION(S): On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.

Adult↗

PubMed1998

Endometrial thickness and oestradiol concentration in women with bleeding complaints during use of Norplant implants.

The objective of this study was to measure oestradiol, progesterone and endometrial development among Norplant implant users with bleeding complaints. Seventy-six volunteers complaining of prolonged/frequent bleeding were enrolled. Oestradiol, progesterone and endometrial thickness (assessed by vaginal ultrasound) were determined at that visit. Two thirds of the women had low oestradiol (< 50 pg/ml) and all except one had low progesterone concentrations (< 3 ng/ml). A total of 68% had a very thin endometrium (< 3 mm). A subgroup of 21 women were followed twice a week for 8 consecutive weeks. Oestradiol and progesterone concentrations remained low during the continuous bleeding episodes or short bleeding-free intervals (< or = 15 days), yet increased five- to sixfold (253.4 +/- 142.2 pg/ml) in long bleeding-free intervals. Endometrial thickness remained thin irrespective of the differences in bleeding patterns and oestradiol. We conclude that Norplant implant users with bleeding complaints are usually characterized by low oestradiol concentrations, absence of luteal activity and thin endometrium. A good correlation exists with increasing oestradiol concentrations and longer bleeding-free intervals, but this is not manifested by increased endometrial thickness. However, few subjects bleed with relatively high oestradiol concentrations, therefore a better understanding of the intimate disturbances related to endometrial bleeding in users of long-acting progestins is still pending.

Contraceptive Agents, Female↗

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

Contraceptives for lactating women: a comparative trial of a progesterone-releasing vaginal ring and the copper T 380A IUD.

From approximately one week before normal ovulation resumes, lactating women require protection against pregnancy by a contraceptive that is safe for both infant and mother in a multicenter one-year study, the natural hormone, progesterone, delivered vaginally by a sequence of four contraceptive rings designed for continuous use, was evaluated as a contraceptive for nursing mothers in comparison with the Copper T 380A IUD. Individual rings release in effective average dose of 10 mg day for a 3 month period. Evaluation included measures of lactational performance as well as of contraceptive efficacy and safety to mother and child. Nine participating clinics enrolled 802 ring users and 734 IUD acceptors between postpartum days 29 and 63. Life table analyses were performed with parallel decrements for ring and IUD subjects. Continuation in the study and analysis required that subjects not stop breastfeeding. The ring, with a one-year pregnancy rate of 1.5 per 100, did not differ significantly from the IUD with respect to contraceptive effectiveness (p > 0.05). More than half of the ring subjects were continuing at 6 months post admission and a quarter (23.5 per hundred) were still using the ring and breastfeeding one year after admission. Women with the IUD, however, had higher continuation rates (p < 0.001) at both time points. The largest single decrement for each method was that for weaning. Ring users had more complaints of vaginal problems but had fewer vaginal disorders on examination. At 12 months postpartum, 46 per 100 continuing ring users remained in amenorrhea. Lactation performance and the health and weight gain of the infants were similar among users of either regimen.

Administration, Intravaginal↗

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↗

PubMed1997

Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan.

There is an urgent need to develop safe, effective, and acceptable vaginal products for the prevention of sexually transmitted infections. Preliminary in vitro results suggest that vaginal formulations of sulfated polysaccharides, including iota-carrageenan, have the potential to block mucosal transmission of human immunodeficiency virus (HIV). Twenty-five women in five sites participated in Phase I trials to evaluate the safety of a formulation containing iota-carrageenan (PC 213). The results of this study indicate that a 5 mL 2% gel formulation of iota-carrageenan is not associated with significant irritation of the female reproductive tract when administered once daily in the absence of sexual intercourse. Given the small number of participants in this initial study, careful observation for potential irritation must also be included in larger studies of this and other vaginal formulations.

Administration, Intravaginal↗

PubMed1997

A comparison of "U" and standard techniques for Norplant removal.

OBJECTIVE: To evaluate the "U" technique versus the manufacturer-recommended technique for Norplant removal. METHODS: We conducted a randomized comparison of the manufacturer-recommended method of removal and the "U" technique. The latter involves an incision between and parallel to the third and fourth implants and uses a modified vasectomy clamp to remove the implants by pulling perpendicular to the implant's axis. RESULTS: Twenty-one physicians (three experienced, 18 inexperienced) performed 200 Norplant removals. Inexperienced physicians took significantly less time for removal using the "U" technique than the standard technique (7.9 versus 10.5 minutes), even after controlling for other factors. Experienced physicians also required less time for removal using the "U" technique (3.1 versus 3.7 minutes), but the difference was not statistically significant after controlling for other factors. Both experienced and inexperienced physicians broke implants more frequently using the standard technique, although the difference was significant only for experienced physicians (relative risk 3.6, 95% confidence interval 1.2, 10.8). No differences were noted between the techniques with respect to tissue damage or patient reports of pain during or after removal. CONCLUSIONS: These results suggest that the "U" technique is an improvement over the standard technique, particularly for personnel who are not highly experienced in Norplant removal.

Adult↗

PubMed1997

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.

Administration, Intravaginal↗

PubMed1996

Multicenter clinical trial on the efficacy and acceptability of a single contraceptive implant of nomegestrol acetate, Uniplant.

Uniplant, a single Silastic implant containing nomegestrol acetate, provides contraceptive efficacy for one year. Uniplant use for one year was studied in 1,803 healthy women of reproductive age, enrolled from 10 centers in 9 countries, after informed consent. Implants were placed subdermally either in the upper arm or in the gluteal region. Two-hundred-seventy-six subjects discontinued prior to completing one year of study. Cumulative discontinuation rate at 12 months was 15.72%. Medical reasons for discontinuation were principally menstrual-related. Fifteen pregnancies occurred during the one year study period, resulting in a 12-month net cumulative pregnancy rate of 0.94%. Approximately 56% of subjects using Uniplant had bleeding patterns similar to normal menstruation. Results from this study confirm that Uniplant is an efficient, well tolerated, 12-month contraceptive implant, with the advantage of easier insertion and removal of the single implant compared to other multiple implant methods.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

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↗

PubMed1996

Results of a user satisfaction study carried out in women using Uniplant contraceptive implant.

A study of the acceptability of Uniplant, a 12-month single implant of nomegestrol acetate, included 819 women from Africa, Latin America, and China, participating in a clinical trial of Uniplant. A standard, pre-coded questionnaire was specially designed for this purpose and applied at the moment of removal of implant, either at the end of 12 months of use or at the time of discontinuation for whatever reason. The level of satisfaction proved high when users' comparison with their previous contraceptive method, users' recommendation of Uniplant to others, users' intention to use the method in the future, and service satisfaction were taken into consideration. Uniplant was considered easy to use, safe (low risk of pregnancy), and also to cause fewer side effects than other methods. When asked about the least liked feature of Uniplant, almost half the respondents said that there was nothing that they disliked and about one-third mentioned the changes in their menstrual pattern. However, according to the clinical trial, over half of the Uniplant users have bleeding patterns similar to untreated cycles. The majority of respondents did not feel any discomfort during the procedure of insertion and removal of the implant. About 70% of patients in the study stated that they required contraception for more than one year and most of these women said that they did not mind having to change the implant every year.

Adult↗

PubMed1996

Effect of preovulatory insertion of Norplant implants over luteinizing hormone secretion and follicular development.

OBJECTIVE: To determine whether the process of ovulation could be interrupted by the insertion of Norplant implants (Leiras Pharmaceuticals, Turku, Finland) in the advanced preovulatory phase. DESIGN: Prospective study. SETTING: The Department of Biomedical Research at the Family Planning Clinic of PROFAMILIA, Santo Domingo, Dominican Republic. PATIENTS: Healthy women of reproductive age, requesting Norplant implants contraception. Thirteen of 15 women volunteers who were admitted completed the study. INTERVENTIONS: Norplant implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based on serial vaginal ultrasounds (US) beginning on day 10 of the cycle. Blood samples for determination of E2, P, LH, and levonorgestrel, were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred at 72 hours after insertion, blood sampling and US were done three times per week during 2 additional weeks. RESULTS: Follicle rupture occurred in 11 of 13 subjects within 72 hours after insertion, with the exception of 1 subject in whom rupture occurred between 72 and 192 hours. Two women already had an LH peak at the time of insertion. In 9 of the remaining 11 women, a shortlasting, blunted LH surge was observed at 4 hours postinsertion. In the remaining two women, who had the lowest E2 levels, ovulation was inhibited, and a persistent follicle developed without luteinization. CONCLUSIONS: The insertion of Norplant implants in the advanced follicular phase will not inhibit ovulation if sufficient E2 priming has occurred. On the contrary, the exogenous progestin may rapidly foster ovulation shortly after.

Drug Implants↗