A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.

STUDY QUESTION: Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day? SUMMARY ANSWER: In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG. WHAT IS KNOWN ALREADY: UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA. STUDY DESIGN, SIZE, DURATION: A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU). PARTICIPANTS/MATERIAL, SETTING, METHODS: A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL). MAIN RESULTS AND THE ROLE OF CHANCE: Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles. LIMITATIONS, REASONS FOR CAUTION: This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images. WIDER IMPLICATIONS OF THE FINDINGS: Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.

Assessment of the use of two new low-dose levonorgestrel-releasing intrauterine systems as contraceptives.

Evaluation of: Gemzell-Danielsson K, Schellschmidt I, Apter D. A randomized, Phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil. Steril. 97(3), 616-622.e3 (2012). A randomized, open-label, Phase II study was conducted in 37 centers in five European countries to assess the optimal dose for a new contraceptive levonorgestrel intrauterine system (LNG-IUS). Overall, 742 parous or nulliparous women aged 21-40 years were allocated to receive a LNG-IUS that initially releases 12 µg/day (LNG-IUS(12)) or 16 µg/day (LNG-IUS(16)) in vitro or the currently available device that releases 20 µg/day (LNG-IUS(20)). The two new devices are shorter than the current one. Pearl Indices of 0.17, 0.82 and 0.00 for the LNG-IUS(12), LNG-IUS(16) and LNG-IUS(20), respectively, reflect the contraceptive efficacy of these devices. The mean number of bleeding and spotting days decreased in all three groups; however, this decrease was more significant in LNG-IUS(20) users. Placement of the new shorter devices was considered simple by providers, while patients reported significantly less pain with the two new devices compared with the current one. This study provided further insight into the development of two new LNG-IUS devices as contraceptives, with the additional possibility of using them to treat heavy menstrual bleeding or as endometrial protection during estrogen therapy.

Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation.

BACKGROUND: The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates. METHODS: In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation. RESULTS: For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days -5 to -1), 16 pregnancies were expected and no pregnancy occurred (p<.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods. CONCLUSION: The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient.

The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium.

OBJECTIVE: To study Cox-2 expression in relation to bleeding patterns in patients using an oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinylestradiol (DRSP/EE). METHODS: Forty-three patients of reproductive age with symptoms of menorrhagia and dysmenorrhoea, who were submitted to endometrial resection, were enrolled. Twelve patients were in the proliferative phase and the remaining 31 were either currently using DRSP/EE or had discontinued its use four to eight days prior to hysteroscopy. Cox-2 and Ki-67 expression were determined in the endometrium using immunohistochemistry. RESULTS: Cox-2 expression was significantly inhibited in the glandular epithelium of patients who became amenorrhoeic during DRSP/EE use; however, in patients with breakthrough bleeding and in those who had stopped oral contraceptive use, a significant increase occurred in Cox-2 expression in the endometrium. Ki-67 expression decreased significantly during DRSP/EE use, but returned to proliferative phase values four to eight days after discontinuation of treatment. CONCLUSION: These results suggest that endometrial bleeding during DRSP/EE use is associated with an increase in Cox-2 expression in the endometrium. A similar increase was also seen four to eight days following discontinuation of the oral contraceptive.

[Emergency contraception with levonorgestrel]. / Contracepción de emergencia con levonorgestrel.

Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate, preventing about 80% of pregnancies. Efficacy is higher the earlier after unprotected intercourse the drug is taken, but it may be administered up to 5 days post-coitum. Tolerance is similar to, or better than, those of other oral emergency contraceptives. Adverse effects include nausea, vomiting, headache, breast tenderness and transient alteration of menstrual bleeding pattern. It is not known whether levonogestrel increases the risk of ectopic pregnancy when the treatment fails. Its use as an ongoing contraceptive method is discouraged. When given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation. It may also affect sperm migration in the female reproductive tract and have an effect on fertilization. Although it has been often postulated, there is no evidence for an anti-implantatory effect. Acquaintance with the method is quite variable among different societies, but it remains underutilized even where it is well known. Advance provision of the drug has been proposed as a way to promote its use. In clinical trials, advance provision did not adversely modify sexual or regular contraceptive behavior, but it did not reduce pregnancy or abortion rate either. Therefore, emergency contraception with levonorgestrel should be regarded as a backup method which is not a substitute for the continued use of more effective contraceptive methods.

Serum anti-mullerian hormone levels and follicular cohort characteristics after pituitary suppression in the late luteal phase with oral contraceptive pills.

BACKGROUND: Anti-mullerian hormone (AMH) is a marker of ovarian function and reserve and reflects the number and size of antral follicles. The objective of this study was to evaluate the effect of FSH suppression on AMH levels, during the late luteal phase of human menstrual cycle, with the use of oral contraceptives pills (OCP). METHODS: Twenty normovulatory infertile women were included in the study. On the third day of a spontaneous menstrual cycle, the patients were submitted to a transvaginal ultrasound examination and blood sample collection. From the 20th day of this menstrual cycle, the patients took daily OCP, containing 0.030 mg of ethinyl-estradiol plus 0.15 mg of desogestrel. On the third day of the following cycle, the measurements were repeated. RESULTS: After OCP use, the levels of FSH and estradiol were significantly reduced (P < 0.001). The number of antral follicles measured on both occasions did not differ, although after OCP use, the follicles presented significantly lower diameters (mean 4.4 + 1.7 mm before OCP versus 3.5 + 1.2 mm after OCP P < 0.001). The levels of AMH were significantly reduced after pituitary suppression, with a median (inter-quartile range) of 3.02 ng/mL (1.21-6.39) before OCP and 2.22 ng/mL (0.9-3.11) after OCP, P = 0.04. CONCLUSIONS: The short administration of OCP in late luteal phase caused suppression of FSH secretion during the cycle transition, leading to a more homogeneous follicular cohort. The lower AMH levels observed, although simultaneous with FSH suppression, were probably not a direct effect of the reduced FSH levels, but were more likely a consequence of the lower production by the arrested follicular cohort.

Contracepción de emergencia con Levonorgestrel / Emergency contraception with levonorgestrel

La contracepción de emergencia puede evitar el embarazo luego de un coito sin medidas contraceptivas o cuando éstas fallan. Se recomienda el levonorgestrel, un gestágeno sintético, en dosis única de 1.5 mg (alternativamente en dos dosis de 0.75 mg espaciadas 12 h). Su eficacia es moderada, pues impide aproximadamente 80% de los embarazos. La eficacia es mayor cuanto más precozmente se administre, pero puede darse hasta 5 días post-coito. La tolerancia es similar o superior a la de otros preparados empleados con igual propósito. Los efectos adversos comprenden náuseas, vómitos, cefalea, tensión mamaria y alteraciones transitorias en la siguiente menstruación. Se desconoce si el levonorgestrel aumenta la probabilidad de embarazo ectópico cuando el tratamiento fracasa. No se recomienda su empleo como contraceptivo habitual. Cuando se administra antes del pico preovulatorio de LH, el levonorgestrel generalmente bloquea o retrasa la ovulación. Puede asimismo afectar la migración de los espermatozoides en el tracto genital femenino e, indirectamente, la fertilización. Pese a haberse postulado reiteradamente, no existe evidencia de un efecto antiimplantatorio. El conocimiento del método es muy variable en diferentes sociedades, pero aun donde es bien conocido permanece subutilizado. Se ha propuesto proveer levonorgestrel por adelantado para promover su uso. En ensayos clínicos, tal provisión no afectó adversamente el comportamiento sexual ni el empleo de otros contraceptivos, pero tampoco redujo el número de embarazos o abortos. En consecuencia, el empleo de levonorgestrel debe considerarse un método de respaldo que no reemplaza el uso de contraceptivos más eficaces.

Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate, preventing about 80% of pregnancies. Efficacy is higher the earlier after unprotected intercourse the drug is taken, but it may be administered up to 5 days post-coitum. Tolerance is similar to, or better than, those of other oral emergency contraceptives. Adverse effects include nausea, vomiting, headache, breast tenderness and transient alteration of menstrual bleeding pattern. It is not known whether levonogestrel increases the risk of ectopic pregnancy when the treatment fails. Its use as an ongoing contraceptive method is discouraged. When given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation. It may also affect sperm migration in the female reproductive tract and have an effect on fertilization. Although it has been often postulated, there is no evidence for an anti-implantatory effect. Acquaintance with the method is quite variable among different societies, but it remains underutilized even where it is well known. Advance provision of the drug has been proposed as a way to promote its use. In clinical trials, advance provision did not adversely modify sexual or regular contraceptive behavior, but it did not reduce pregnancy or abortion rate either. Therefore, emergency contraception with levonorgestrel should be regarded as a backup method which is not a substitute for the continued use of more effective contraceptive methods.

Emergency contraception in Cuba with 10 mg of mifepristone.

BACKGROUND: Mifepristone in a dose of 10 mg is an effective emergency contraceptive when administered up to 120 hours after unprotected coitus. METHODS: Between May 2003 and February 2005, we conducted in Cuba a single-arm trial to evaluate the effectiveness of 10 mg mifepristone for emergency contraception up to 6 days after unprotected coitus. A total of 635 women who requested emergency contraception after a single act of unprotected intercourse were included in the study. RESULTS: After treatment there were 7/635 (1.1%) pregnancies (95% CI 0.4-2.3%). Pregnancy that might have occurred was prevented in 88.0% of the cases (95% CI 77.1-95.1%). The most common side effects reported by participants were fatigue (10.7%), dizziness (6.1%) and nausea (4.9%); vomiting was only reported by 0.6%. In 38/635 (6.0%) women menstruation was delayed more than 7 days. CONCLUSIONS: Mifepristone 10 mg administered is an effective emergency contraceptive with an acceptable profile of side effects up to five days, but greater studies are necessary to verify its efficacy up to 6 days after unprotected intercourse.

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.

Therapeutic use of levonorgestrel-releasing intrauterine system in women with menorrhagia: a pilot study(1).

The objective of this study was to evaluate the efficacy and performance, for up to 1 year, of an intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS, Mirena) in the treatment of women with menorrhagia. It was a descriptive, prospective, non-comparative study. A 20 microg/day LNG-releasing-IUS was inserted on any day during bleeding to 44 women (between 24 and 49 years of age) who presented with menorrhagia after medical therapies had failed. Menstrual patterns were assessed, and hemoglobin concentrations were measured before LNG-IUS was inserted and at 3, 6, 9, and 12 months of use. The most common bleeding pattern at 3 months after insertion was spotting, and after 6, 9, and 12 months the majority of women presented with amenorrhea or oligomenorrhea. Three women requested removal of the LNG-IUS because of spotting, and six women expelled it spontaneously. Hemoglobin levels were improved from 102 g/L to 123 and 128 g/L at 3 and 12 months, respectively, after insertion of the LNG-IUS (p < 0.01). At 12 months 79.5% of participants continued the use of LNG-IUS. In conclusion, LNG-IUS was an effective treatment for three out of four women with menorrhagia and could be an alternative treatment for women with menorrhagia who are either contraindicated for or refuse hysterectomy or endometrial ablation.

Third-generation progestogen type influences hemostatic changes caused by oral contraceptives in Brazilian women.

We compared the effects of two third-generation progestogens, desogestrel (DSG) and gestodene (GSD), on coagulation and fibrinolysis in Brazilian users of oral contraceptives (OCs). Forty-six women were evaluated before treatment and after six cycles of treatment. The coagulation, anticoagulant, and fibrinolytic systems were investigated. During the use of the DSG-containing OC, the activity of factors VII, VIII, IX, X, and XII increased significantly whereas the GSD-containing OC caused no changes in coagulation parameters. Concerning the anticoagulant pathways, the DSG-containing OC increased protein C levels and decreased total protein S levels, and the GSD-containing OC only decreased total protein S. Both OCs increased plasminogen activity, although the DSG-containing OC increased fibrin degradation products levels and decreased the tissue plasminogen activator antigen. In conclusion, we have found that in Brazilian women the effects of DSG and GSD on hemostatic parameters are different and, therefore, third-generation progestogens may not contribute equally to the thrombotic risk.

Morphological and functional study of the cochlea after administration of estrogen and progesterone in the guinea pig.

The aim of this study was to analyze the morphological cochlear changes and auditory function observed after the administration of estrogen or progesterone or both. Sixty-two guinea pigs were divided into four groups that received estrogen (group 1), progesterone (group 2), estrogen and progesterone (group 3), and saline solution (controls, group 4), respectively. The auditory evaluation consisted of brainstem evoked response audiometry, performed before and after drug administration. Structural analysis was based on histological hematoxylin and eosin staining preparations. Our results showed changes in latency and amplitude of waves in the study groups that received estrogen or progesterone. The main histological changes observed were inflammatory infiltrate and vacuolization of the stria vascularis. Our results suggest that both estrogen and progesterone lead to morphological and physiological lesions of the cochlea, the degree of the observed lesions depending not only on the presence of these hormones but also on the proportion between them.

Eficácia, tolerabilidade, controle de ciclo e bem-estar em mulheres acima de 35 anos utilizando um contraceptivo de baixa dose contendo gestodeno e etinilestradiol (Harmonet) / Efficacy, tolerability, cycle control and welfare in woman above 35 years using a low dose contraceptive containing gestodene and ethynilestradiol (Harmonet)

Um estudo multicêntrico foi conduzido em 14 centros brasileiros para avaliar a eficácia, tolerabilidade, controle de ciclo e bem-estar em mulheres, não fumantes, acima de 35 anos utilizando um contraceptivo de baixa dose contendo gestodeno e etinilestradiol, durante seis ciclos de tratamento. Participaram do estudo 180 mulheres na faixa etária de 35 a 47 anos, das quais 158 (87,8 por cento) completaram os seis ciclos de tratamento. Nenhuma gravidez ocorreu entre as usuárias do contraceptivo em estudo. Um total de 950 ciclos foi avaliado. Em 92,5 por cento dos ciclos não houve spotting nem sangramento de escape. Ocorreu spotting em 7,2 por cento dos ciclos e sangramento de escape em 0,3 por cento dos ciclos. Com relação ao número de mulheres, 82,2 por cento não apresentaram spotting nem sangramento de escape em nenhum momento do ciclo. Observou-se uma diminuição significativa, indicativa de melhora, com relação ao pré-tratamento, nos escores do questionário de Moos de desconforto menstrual relativos a dor, concentração, mudanças comportamentais, afeto negativo, reações autonômicas, retenção hídrica e controle. Não houve alterações clinicamente significativas de peso, pressão arterial nem resultados laboratoriais. A adesão ao tratamento foi boa, tendo havido esquecimento de tomada de uma ou mais pílulas em apenas 3 por cento do total de ciclos; 12,2 por cento das mulheres não completaram o período de seis ciclos de tratamento, sendo que em 1,1 por cento dos casos a razão para descontinuação foi atribuída a efeitos adversos. Os resultados permitem concluir pela eficácia contraceptiva, bom controle de ciclo, tolerabilidade e bem-estar associados ao uso do contraceptivo de baixa dose contendo gestodeno e etinilestradiol em mulheres acima de 35 anos.

Effects of long-term low-dose mifepristone on reproductive function in women.

Low-dose antiprogestin administration has been proposed as a new contraceptive modality to interference with endometrial receptivity without disturbing ovarian function. The effects of 1 mg/day mifepristone for 150 days on the menstrual cycle were assessed in 21 surgically sterilized women. The aim was to study each woman for one control cycle and during months 1, 3 and 5 of treatment. Ovulation, endometrial thickness, serum oestradiol and progesterone, urinary luteinizing hormone, endometrial morphology and cervical mucus were assessed. Luteal phase progesterone concentrations were observed in 36 of the 60 treated months assessed and less frequently as treatment progressed. The bleeding pattern was regular in most biphasic cycles, while prolonged interbleeding intervals or no bleeding were associated with monophasic cycles. Altered endometrial morphology was found in all cases irrespective of the occurrence of luteal activity. Increased endometrial thickness and dilated glands were observed in 25 and 34% respectively of the monophasic cycles. Mifepristone, 1 mg/day, interferes with endometrial development while allowing the occurrence of biphasic ovarian cycles and regular bleeding. However, it also prevents ovarian cyclicity in a high proportion of treated months, and this is associated with increased endometrial growth in some women, which may be of concern.

PIP: Low-dose antiprogestin administration has been proposed as a new contraceptive modality that interferes with endometrial receptivity without disturbing ovarian function. To explore this potential, the effects on the menstrual cycle of 1 mg/day of mifepristone for 150 days were assessed in 21 surgically sterilized women from Santiago, Chile. Control cycles were biphasic in all 21 women and ovulatory in 20 women. Luteal phase progesterone concentrations were observed in 36 of the 60 treatment months (1, 3, and 5) assessed. The proportion of ovulatory cycles was highest during month 1 and decreased progressively with treatment. 40% of treatment cycles were monophasic and bleeding cyclicity was altered in 57%. Prolonged inter-bleeding intervals or no bleeding occurred in monophasic cycles. Endometrial morphology was altered in all cases, regardless of the occurrence of luteal activity. Increased endometrial thickness and dilated glands were recorded in 25% and 34%, respectively, of the monophasic cycles. These findings suggest that 1 mg of mifepristone interferes with endometrial development while allowing biphasic ovarian cycles and regular bleeding. Whether these endometrial alterations are sufficient to prevent implantation remains to be established. The long-term effect of prevention of ovarian cyclicity and the associated increased endometrial growth recorded in some women require further investigation.

[Postabortion contraception]. / Anticoncepción postaborto.

In Mexico, as in almost all the Latin American countries, abortion represents an important maternal morbidity-mortality reason. It has been pointed out that those women who had an abortion, are in greater risk to repeat this condition than those women who have not had the episode. For this reason, it is a transcendental matter, the use of modern contraceptive technology for fertility regulation with the aim to avoid not planned pregnancies and their devastating consequences. This document reviews-according to the Family Planning Official Norm of the Ministry of Health-those different contractive alternatives, that can be used in the postabortion.

Anticoncepción postaborto / Postpartum anticonception

El embarazo incrementa el riesgo de eventos isquémicos cerebrovasculares. La trombosis del seno longitudinal es muy rara, pero la incidencia aumenta en el embarazo y el puerperio. La mortalidad es de 25 a 50 por ciento, se presenta un caso estudiado y maneja en el Hospital Central Militar. Se presentó durante el décimosegundo día postcesárea; en diagnosticó se corroboró con estudio de Resonancia Magnética Nuclear, se trató a base de heparina y reposo, evaluacionando satisfactoriamente. Lo cual coincide con estudios retrospectivos recientes que sugieren que existe un efecto benéfico con el uso de heparina, disminuyendo drásticamente la mortalidad. Aunque existen investigadores que se oponen por la posibilidad de hemorragia intracraneana

Fertility regulation in nursing women. IX. Contraceptive performance, duration of lactation, infant growth, and bleeding patterns during use of progesterone vaginal rings, progestin-only pills, Norplant implants, and Copper T 380-A intrauterine devices.

This study evaluated the performance of progesterone vaginal rings (n = 187), progestin-only pills (n = 117), Norplant implants (n = 120), and Copper T 380-A intrauterine devices (n = 122) in lactating women. Contraceptive efficacy, bleeding pattern, and influence of the method upon breastfeeding duration and infant growth were compared with those of untreated women (n = 236) who relied on lactational infertility. Participants were healthy, 18 to 38 years, had had a normal delivery, and were intending to breastfeed for as long as possible. Contraceptives were initiated at day 57 +/- 3 postpartum. Results are reported for the first year of use. All methods were highly effective, with pregnancy rates below 1%. None affected breastfeeding performance or the rate of infant growth. Users of the progestin-only methods experienced a period of lactational amenorrhea 4 to 5 months longer than did users of Copper T or untreated women. More than half of the women in each contraceptive group reported a bleeding in the first month after treatment initiation, which was not considered in the calculation of the duration of amenorrhea. Prolonged or frequent bleedings were infrequent. The proportion of bleedings lasting more than 10 days ranged from 0 in the progestin-only pills group to 7% in the Norplant implants group. The four methods, initiated around the eighth postpartum week, provided effective contraception with no negative effects upon lactation or infant growth and without the bleeding problems associated with their use in nonlactating women.

[Endometrial interference of synthetic estrogens in fertility regulation.Is it necessary to interfere with the antiovulatory mechanism at the central nervous system level in order to obtain contraception?]. / Interferencia endometrial de los estrógenos sintéticos en la regulación de la fertilidad. Es necesario el mecanismo antiovulatorio a nivel del sistema nervioso central, para obtener la anticoncepción?

For some time the anti-ovulatory activity of certain estrogen/progestagen preparations was the main approach in fertility control. Up to date a drastic dosage reduction of both steroid hormones has been accomplished ameliorating the side effects on the one hand, and being active compounds as contraceptives, in the other. Currently, there are a wide variety of oral contraceptives available with a variety of estrogen doses combined with different progestagens. The estrogen content is a high as 80 micrograms and as low as 20 micrograms, moreover, such formulations are prescribed beginning the 1st or the 5th day of the menstrual cycle. By studying plasma and endometrial samples simultaneously obtained from chronic oral contraceptive users taking either 30 micrograms or 50 in such pills; a 17-beta-estradiol pattern was attained as that seen during follicular maturation in the ovulatory cycle only women under the lower dose of synthetic estrogen. However, in the endometrium such a cyclicity did not take place; in parallel circulating progesterone in both groups never reach levels greater than 5.0 ng/ml. Results offer to find a local critical period during the ovulatory menstrual cycle to achieve with much lower hormonal dosages a different approach in future methods of contraception.