Persistent vaginal bleeding during gender-affirming hormone therapy in transgender men.

PURPOSE: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition. METHODS: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months. RESULTS: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019). CONCLUSION: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.

A randomized controlled pilot study of ulipristal acetate for abnormal bleeding among women using the 52-mg levonorgestrel intrauterine system.

OBJECTIVE: To assess the efficacy of ulipristal acetate (UPA) for reducing abnormal bleeding among women using the 52-mg levonorgestrel intrauterine system (LNG-IUS). METHODS: A randomized, double-blind, placebo-controlled pilot study conducted from September 1, 2016 to September 30, 2018, at the University of Campinas, Brazil. LNG-IUS users reporting prolonged or frequent uterine bleeding for at least 1 year were randomized to receive 5 mg UPA per day for 5 days or placebo at an identical regimen. Bleeding was recorded for 90 days after treatment began and was compared between the groups. RESULTS: Of 94 eligible women, 64 with abnormal bleeding associated with LNG-IUS use declined treatment or device removal after counselling regarding anticipated bleeding patterns. For the 25 study participants, differences were nonsignificant between the UPA and placebo groups for number of days before bleeding stopped and days free of bleeding; however, UPA users displayed a trend for shorter duration before bleeding stopped and longer time free of bleeding. A similar trend for mean number of bleeding days at 30-, 60-, and 90-day follow-up was observed. CONCLUSION: A nonsignificant trend in reduction of abnormal bleeding was observed among LNG-IUS users taking 5 mg UPA per day for 5 days compared with placebo; however, further research is needed. CLINICALTRIALS.GOV: NCT03186586.

[Combined hormonal contraception in cycles artificially extended]. / Anticoncepción con hormonales combinados en ciclos extendidos artificialmente.

OBJECTIVE: To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. MATERIAL AND METHODS: Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. CONCLUSION: Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.

Manejo do sangramento inesperado em usuárias de métodos contraceptivos hormonais: revisão das recomendações atuais / Management of unscheduled bleeding in women using hormonal contraceptive: review of current recommendations

Os objetivos desta revisão foram identificar e analisar as principais recomendações atuais relativas ao manejo do sangramento inesperado em usuárias de anticoncepcional hormonal. Foram revisadas as principais diretrizes publicadas nos últimos dez anos. Quatro bases de dados eletrônicas foram consultadas (Medline, LILACS, Scielo, CINAHL®). De um total inicial de 14.130 citações, 14 foram selecionadas para inclusão. As principais recomendações sugerem que as mulheres que optam por métodos hormonais devem ser orientadas quanto à possibilidade da ocorrência de sangramentos inesperados. Tais sangramentos podem desaparecer espontaneamente com a persistência no uso do método. Na maioria das vezes, esta intercorrência não afeta a eficácia anticonceptiva do método, e recomenda-se não criar a expectativa de que irá ocorrer amenorreia na vigência do uso de métodos contraceptivos hormonais. Esta revisão pode ser útil na prática clínica, dada a importância do tema e a frequência desse tipo de queixa nos ambulatórios de tocoginecologia

The objectives of this review were to identify and analyze the main current recommendations on the management of unscheduled bleeding in women using hormonal contraceptives. The main guidelines published during the last ten years were reviewed. Four electronic databases were consulted (Medline, LILACS, Scielo, CINAHL®). From the total of 14,130 citations, 14 were selected for inclusion. The main recommendations suggest that women using hormonal contraceptives should be informed about the possible occurrence of unscheduled bleeding. This bleeding may disappear spontaneously with the persistent use of the method. Most of the time this event do not affect the contraceptive effectiveness of the method, and women should not expect the amenorrhea during the use of hormonal contraceptive methods. This review can be useful for clinical practice, considering the importance of this topic and the frequency of this kind of complaint in tocogynecology clinics

Bleeding during oral anticoagulant therapy: warning against a greater hazard.

BACKGROUND: Bleeding is one of the main concerns in patients undergoing oral anticoagulation therapy. OBJECTIVE: To investigate the determinant causes of bleeding in patients undergoing oral anticoagulant therapy. METHODS: A total of 360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo) therapy, with a target INR of 2.0-3.5, were followed prospectively for a period of 48 +/- 7.2 months. The patients were evaluated on average every 30 days and were investigated regarding the presence of associated pathology that could lead to bleeding. RESULTS: A total of 338 patients participated in the present study. Of these, 210 (62.13%) were females. Mitral stenosis was present in 218 patients (64.4%), a mitral biological prosthesis in 64 (18.9%) and mitral valve failure in 56 (16.5%) patients. Bleeding occurred in 65 patients (19.2%), being severe in 7 (10%) patients. In 38/65 patients, a new associated disease was identified, which facilitated bleeding. An associated disease was identified in 100% of the patients with bleeding within the therapeutic range, against 49.05% of associated disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION: The diagnosis of a local disease associated to the bleeding was frequent among those patients undergoing oral anticoagulant therapy (58.5%). There was an association between bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate the cause of bleeding in patients undergoing oral anticoagulant therapy, especially if the INR is within the therapeutic range.

Sangramento durante a anticoagulação oral: alerta sobre um mal maior / Sangrado durante la anticoagulación oral: alerta sobre un mal mayor / Bleeding during oral anticoagulant therapy: warning against a greater hazard

FUNDAMENTO: Sangramento é uma das grandes preocupações em pacientes sob anticoagulação oral. OBJETIVO: Investigar causas determinantes do sangramento em usuários de anticoagulante oral. MÉTODOS: Foram acompanhados prospectivamente, por 48 ± 7,2 meses, 360 pacientes com fibrilação atrial (FA), todos em uso de anticoagulante oral (ACo) com INR-alvo de 2,0-3,5, avaliados em média a cada 30 dias. Os pacientes foram investigados quanto à presença de patologia associada que levasse a sangramento. RESULTADOS: Participaram deste estudo 338 pacientes. Desses, 210 (62,13 por cento) eram do sexo feminino. A estenose mitral estava presente em 218 pacientes (64,4 por cento), a prótese biológica mitral em 64 (18,9 por cento) e a insuficiência da valva mitral em 56 (16,5 por cento). O sangramento ocorreu em 65 pacientes (19,2 por cento) e de forma grave em 7 (10 por cento). Em 38/65 pacientes (58,5 por cento), identificou-se nova doença associada, facilitadora do sangramento. Em 100 por cento dos pacientes com sangramento na faixa terapêutica, foi encontrada doença associada, contra 49,05 por cento de diagnóstico de doenças associadas naqueles com INR > 3,5 (p = 0,001). CONCLUSÃO: O diagnóstico de doença local associada ao sangramento foi frequente entre os medicados com anticoagulante oral (58,5 por cento). Houve associação entre sangramento com INR na faixa terapêutica (INR 2,0-3,5) e diagnóstico de patologia predisponente a sangramento (p < 0,001). Em pacientes em uso de anticoagulante oral que apresentam sangramento, é mandatória a investigação da causa, sobretudo se a INR estiver na faixa terapêutica.

BACKGROUND: Bleeding is one of the main concerns in patients undergoing oral anticoagulation therapy. OBJECTIVE: To investigate the determinant causes of bleeding in patients undergoing oral anticoagulant therapy. METHODS: A total of 360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo) therapy, with a target INR of 2.0-3.5, were followed prospectively for a period of 48 ± 7.2 months. The patients were evaluated on average every 30 days and were investigated regarding the presence of associated pathology that could lead to bleeding. RESULTS: A total of 338 patients participated in the present study. Of these, 210 (62.13 percent) were females. Mitral stenosis was present in 218 patients (64.4 percent), a mitral biological prosthesis in 64 (18.9 percent) and mitral valve failure in 56 (16.5 percent) patients. Bleeding occurred in 65 patients (19.2 percent), being severe in 7 (10 percent) patients. In 38/65 patients, a new associated disease was identified, which facilitated bleeding. An associated disease was identified in 100 percent of the patients with bleeding within the therapeutic range, against 49.05 percent of associated disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION: The diagnosis of a local disease associated to the bleeding was frequent among those patients undergoing oral anticoagulant therapy (58.5 percent). There was an association between bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate the cause of bleeding in patients undergoing oral anticoagulant therapy, especially if the INR is within the therapeutic range.

FUNDAMENTO: El sangrado es una de las grandes preocupaciones en pacientes bajo anticoagulación oral. OBJETIVO: Investigar causas determinantes del sangrado en usuarios de anticoagulante oral. MÉTODOS: Se realizó el seguimiento, prospectivamente, por 48 ± 7,2 meses, de 360 pacientes con fibrilación atrial (FA), todos en uso de anticoagulante oral (ACo) con INR-objetivo de 2,0-3,5, evaluados en promedio cada 30 días. Los pacientes se investigaron sobre la presencia de patología asociada que llevara al sangrado. RESULTADOS: Participaron en este estudio 338 pacientes. De ellos, 210 (62,13 por ciento) eran del sexo femenino. La estenosis mitral estaba presente en 218 pacientes (64,4 por ciento), la prótesis biológica mitral en 64 (18,9 por ciento) y la insuficiencia de la válvula mitral en 56 (16,5 por ciento). El sangrado ocurrió en 65 pacientes (19,2 por ciento) y de forma grave en 7 (10 por ciento). En 38/65 pacientes (58,5 por ciento), se identificó nueva enfermedad asociada, facilitadora del sangrado. En el 100 por ciento de los pacientes con sangrado en el intervalo terapéutico, se encontró enfermedad asociada, contra el 49,05 por ciento de diagnóstico de enfermedades asociadas en aquellos con INR > 3,5 (p = 0,001). CONCLUSIÓN: El diagnóstico de enfermedad local asociada al sangrado fue frecuente entre los medicados con anticoagulante oral (58,5 por ciento). Hubo asociación entre sangrado con INR en el intervalo terapéutico (INR 2,0-3,5) y diagnóstico de patología predisponente a sangrado (p < 0,001). En pacientes en uso de anticoagulante oral que presentan sangrado, es indispensable la investigación de la causa, sobre todo si la INR está en el intervalo terapéutico.

Cyclooxygenase-2 expression in the endometrium and its relationship to bleeding in users of continuous oral contraceptives.

OBJECTIVE: The objective of the present study was to investigate whether or not the presence of irregular bleeding during use of oral contraceptives (OC) is associated with increased cyclooxygenase-2 (COX-2) expression. PATIENTS AND METHODS: An observational study was carried out in 26 patients who were using gestodene 75 microg/ethinylestradiol 30 microg prior to endometrial resection. The patients were divided into two groups: those with amenorrhea (n = 14) and those who had irregular bleeding (n = 12). The resected endometrium was immunostained for COX-2, Bcl-2 and Ki-67 expression. Routine pathology was carried out using standard hematoxylin-eosin staining. RESULTS: Irregular bleeding during OC use was associated with strong COX-2 expression in both glandular and superficial epithelium. There were also more patients in this group with irregular endometrial maturation and higher Ki-67 values. Bcl-2 expression, on the other hand, was not affected by the presence of uterine bleeding. CONCLUSION: The presence of irregular bleeding during OC use is associated with strong COX-2 expression in the endometrium, thereby suggesting a pivotal role of prostaglandins in this process.

Effectiveness and acceptability of vitamin E and low-dose aspirin, alone or in combination, on Norplant-induced prolonged bleeding.

A study (ISRCTN 77665712) was undertaken to test the effectiveness and the acceptability of vitamin E and low-dose aspirin, alone or in combination, as treatment for prolonged vaginal bleeding induced by Norplant. A total of 486 Norplant users who were requesting treatment for bleeding lasting longer than 7 days were enrolled in five centers: Beijing, China; Jakarta, Indonesia; Santiago, Chile; Santo Domingo, Dominican Republic; and Tunis, Tunisia. They were randomized to one of four different 10-day oral treatments: 200 mg vitamin E daily, 80 mg aspirin daily, both or a placebo. Treatment packs were designed to ensure blinding of both the subjects and the clinical staff. Neither vitamin E nor low-dose aspirin nor their combination was found to have any effect on reducing the length of the bleeding episode for which treatment was taken or on the vaginal bleeding patterns these women experienced during the year of follow-up.

Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users.

A double-blind, placebo-controlled, randomized trial, was carried out in 120 Norplant users to evaluate the effect of mifepristone, 100 mg/day administered for 2 consecutive days every 30 days, on the vaginal bleeding pattern. Treatment was given from months 2-7 of implant use. Volunteers recorded bleeding and spotting days, during treatment and for the ensuing 6-month period. During treatment, women on mifepristone recorded the same frequency of bleeding/spotting episodes but significantly less prolonged bleeding episodes than placebo controls (mean +/- SD: 11 +/- 3 vs. 22 +/- 23 days) and their total number of bleeding days was 35% lower than in the placebo group. After the end of mifepristone use, bleeding patterns were similar in both groups. One pregnancy occurred in the mifepristone-treated group, in month 6 of treatment, the outcome was a healthy male baby. We conclude that intermittent administration of mifepristone can offer a clinically significant improvement of the vaginal bleeding pattern in Norplant users.

Vaginal administration of allopregnanolone to postmenopausal women undergoing estrogen replacement therapy: preliminary results.

OBJECTIVE: To assess the tolerability and endometrial effects of vaginal administration of an allopregnanolone gel to postmenopausal women undergoing estrogen therapy. METHODS: Thirteen postmenopausal women included in the study were divided into two groups and submitted to two consecutive cycles of 28 days during which they received 2 mg oral estradiol valerate daily and vaginally administered allopregnanolone gel during the last 10 days of the second cycle (group 1) or during the last 10 days of each cycle (group 2). Systemic adverse effects, vaginal bleeding and endometrial histology were characterized, with group 1 patients being submitted to two endometrial biopsies (days 28 and 56) and group 2 patients to one biopsy (day 56). RESULTS: Five patients did not show any adverse effect. Mastalgia was the most frequently reported adverse effect (four cases), followed by headache and abdominal pain (two cases each). The adverse effects were mild and did not interfere with the adequate use of the medication prescribed. Vaginal bleeding due to deprivation was observed in three of the seven patients submitted to one treatment cycle with allopregnanolone (group 1) and in two of six patients submitted to two treatment cycles (group 2). Endometrial biopsy findings did not suggest any secretory action after exposure to allopregnanolone. CONCLUSIONS: Tolerability of vaginal administration of allopregnanolone gel was good. Studies employing a larger series and longer time of follow-up are necessary to determine the endometrial effects of this drug.

Contraceptive efficacy and clinical performance of Nestorone implants in postpartum women.

The objective of this study was to evaluate the contraceptive efficacy and clinical performance of a Nestorone subdermal implant (NES) in the postpartum period. NES (n = 100) and Copper T intrauterine device (T-Cu; n = 100) acceptors initiated contraception at 8 weeks postpartum and were followed at monthly intervals during the first year and at 3-month intervals thereafter. Pregnancy rates, breastfeeding performance, infant growth, bleeding pattern, and side effects were assessed. Blood and milk NES concentration were measured. No pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use, respectively. No effect of NES on lactation and infant growth and no serious adverse events were observed. Lactational amenorrhea was significantly longer in NES users (353 +/- 20 days) than in T-Cu users (201 +/- 11 days). More NES users (55.8%) experienced prolonged bleedings than did T-Cu users (36.2%). Concentrations of NES in breast milk ranged between 54-135 pmol/liter. The Nestorone implant is a highly effective contraceptive, safe for breastfed infants because the steroid is inactive by the oral route.

Efficacy, acceptability, and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate.

A total of 1,904 women, aged 15-38, used an injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given once during each menstrual cycle between the 7th and 10th day, and preferably on the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women, 1,197 completed 12 cycles of use of the injectable combination. One subject became pregnant during the trial, resulting in a cumulative pregnancy rate of 0.07%. Principal reasons for discontinuation were personal, non-medical reasons, such as lost to follow-up, no longer wished to continue, protocol violation, desire to change to another contraceptive method, moved away, or other personal reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2 kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately 50% of subjects experienced menstrual bleeding similar to normal throughout the study period. The most frequent menstrual abnormality was irregular bleeding, experienced by approximately one-third of subjects.

Premenopause contraception with monthly injectable Mesigyna with special emphasis on serum lipid and bone density patterns.

This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete lipoprotein assessment was carried out before treatment and at 6, 12, and 24 months of treatment. A bone densitometry was performed on half of the women, and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year. No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD. The incidence of bleeding anomalies was higher in the Mesigyna group, with a discontinuation rate for these reasons of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups. No patient developed endometrial hyperplasia after treatment, thus endometrial risk seemed not to be increased. Total and LDL cholesterol, and apolipoproteins did not show modifications. A slight decrease in total triglycerides, HDL and HDL(2) cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women. Mesigyna proved to be a highly effective and low risk agent for premenopausal users.

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.

Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene.

OBJECTIVE: To assess the contraceptive efficacy, cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene. METHODS: In a randomized, open-label, six-cycle, group-comparative, multicenter study performed in Brazil, pregnancies, cycle-control parameters, incidence of side-effects and the presence and severity of acne vulgaris were assessed, and blood pressure and body weight were measured at pretreatment and after one, three and six cycles of oral contraceptive use. RESULTS: Of the 595 women enrolled, 274 (86.7%) in the desogestrel/ethinylestradiol group and 227 (81.4%) in the gestodene/ethinylestradiol group completed the six cycles, providing data for 1753 and 1487 treatment cycles, respectively. Two pregnancies occurred, one of which (in the desogestrel/ethinylestradiol group) was attributed to user failure, whilst the other (in the gestodene/ethinylestradiol group) was thought to result from method failure. Cycle control was observed to be excellent; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle. Pre-existing acne improved in both groups, whereas blood pressure and body weight remained essentially unchanged. CONCLUSIONS: Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability.

Contraceptive efficacy and acceptability of a monophasic oral contraceptive containing 30 microg ethinyl estradiol and 150 microg desogestrel in Latin-American women.

Contraceptive efficacy, subject acceptability (cycle control, side-effects, acne score and weight gain) and blood pressure of a monophasic oral contraceptive containing 30 microg ethinyl estradiol plus 150 microg desogestrel (Marvelon) were assessed in an open-label 6-cycle multicenter study in Argentina (7 centers) and Venezuela (5 centers). Of the 407 participating women, 389 (95.6%) completed six cycles of treatment, providing data for a total of 2383 cycles. No pregnancies occurred during the course of the study, confirming the high contraceptive reliability of Marvelon. Cycle control was excellent; the duration of withdrawal bleeding decreased during consecutive treatment cycles and the incidence of spotting and breakthrough bleeding was low. The desogestrel/ethinyl estradiol combination was well tolerated and the incidence of minor side-effects, which was already low in the first treatment cycle, in most cases decreased during the subsequent cycles. The preparation was effective in reducing pre-existing acne, whereas it did not induce clinically relevant changes in blood pressure and body weight. Marvelon was shown to provide effective oral contraception, with good tolerance and excellent cycle control in Latin-American women.

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.

Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate.

Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.