BACKGROUND: It is estimated that about 40% of pregnancies in the world are unintended and that the major part of these are unwanted. There are several reasons no or ineffective contraception is used to prevent these pregnancies, including difficulty in obtaining contraceptives. The lactational amenorrhoea method (LAM) is a contraceptive method where the mother is informed and supported in how to use breastfeeding for contraception. LAM is available and accessible to many women. OBJECTIVES: To assess the effectiveness of LAM, as defined in the 1988 Bellagio Consensus statement, as a contraceptive method in fully breastfeeding women, who remain amenorrheic, using pregnancy and menstruation life tables. SEARCH METHODS: We searched MEDLINE, EMBASE, POPLINE, and LILACS to 10 October 2014; reference lists of studies; review articles; books related to LAM; published abstracts from breastfeeding, reproductive health conferences; e-mails with study coordinators. SELECTION CRITERIA: Out of 459 potentially relevant studies, 159 investigated the risk of pregnancy during LAM or lactational amenorrhoea. Our inclusion criteria were as follows: prospective study; cases (intervention group) and, if available, controls, had to be sexually active; pregnancy had to be confirmed by physical examination or a pregnancy test. Our endpoints were life table menstruation rates and life table pregnancy rates. We included 15 studies reporting on 11 intervention groups and three control groups. We identified one additional uncontrolled study in the 2007 update and one additional controlled study in this 2015 update. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, resolving disagreements through discussion. We analysed the studies using narrative methods because of their heterogeneity. MAIN RESULTS: For the primary outcome, pregnancy, two controlled studies of LAM users reported life table pregnancy rates at six months of 0.45% and 2.45%, one controlled study reported 5% pregnancies in the absence of life table rates per month, and eight uncontrolled studies of LAM users reported pregnancy rates of 0% to 7.5%. Life table pregnancy rates for fully breastfeeding women who were amenorrheic but not using any contraceptive method were 0.88% in one study and 0.9% to 1.2% (95% confidence interval 0.0 to 2.4) in a second study, depending on the definition of menstruation used. The life table menstruation rate at six months in all studies varied between 11.1% and 39.4%. AUTHORS' CONCLUSIONS: We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. As the length of lactation amenorrhoea in women using LAM differed greatly between the populations studied, and was population specific, it is uncertain whether LAM extends lactational amenorrhoea.

To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive--extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy.

OBJECTIVE: To determine the efficacy of the lactational amenorrhea method of family planning (amenorrhea during full or nearly full breastfeeding for 6 months postpartum). DESIGN: Prospective noncomparative study. SETTING: Normal breastfeeding women in Karachi and Multan, Pakistan, most delivered at home by a midwife. PATIENTS: Three hundred ninety-nine newly delivered mothers who successfully had breastfed a previous child and chose the lactational amenorrhea method to prevent a subsequent pregnancy, 391 of whom were followed for a full year. INTERVENTIONS: Mothers were taught, before or shortly after delivery, to use the method and were interviewed in their homes each month by a Lady Health Visitor. MAIN OUTCOME MEASURE: Life-table pregnancy rates. Periods of postpartum or lactational abstinence were excluded in the calculation of the pregnancy rates. RESULTS: During full or nearly full breastfeeding, while the women were amenorrheic and not otherwise contracepting, the rate of pregnancy was 0.6%. The pregnancy rate during lactational amenorrhea alone was 1.1% at 1 year postpartum. CONCLUSION: The lactational amenorrhea method was found to be highly effective for 6 months. A high degree of contraceptive protection endures for a full year during lactational amenorrhea, but not after the return of menses during breastfeeding.

BACKGROUND: There is still a great deal of controversy with regard to the prognostic role of chemotherapy- induced amenorrhea (CIA) in breast cancer patients. To confirm whether CIA can serve as a useful factor in predicting clinical effects of systemic adjuvant chemotherapy, we performed this meta-analysis. MATERIALS AND METHODS: Relevant studies were identified using PubMed, and Embase databases. Eligible study results were pooled and summary hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated. Subgroup analyses and an assessment of publication bias were also conducted. RESULTS: A total of 8,333 patients from 11 published studies were identified through searching the databases. The pooled HRs for disease-free survival (DFS) suggested that CIA was associated with a significant reduction in the risk of recurrence, especially in patients with hormone receptor-positive lesions (overall HR=0.65, 95%CI 0.53-0.80, I2= 41.3%). When the five studies reporting the HR for overall survival (OS) were pooled (n=4193), a favorable trend was found (HR=0.69, 95%CI 0.52-0.91, I2= 51.6%). No publication bias was observed in this study. CONCLUSIONS: This meta-analysis suggests that CIA predicts a better outcome in premenopausal hormone receptor-positive breast cancer patients.

La amenorrea hipotalámica funcional (AHF)presenta un proceso de adaptación homeostática frente al disbalance energético (consumo/gasto calórico) . En este síndrome participan hormonas hipotalámicas y neuropéptidos periféricos provenientes del tejido graso (leptina, adiponectina y otras adipokinas), el tracto gastrointestinal superior Ghrelin y el páncreas (insulina). Este "circuito periférico” está funcionalmente interrelacionado con un "circuito central "o hipotalámico. El descenso de la leptina, (un péptido anorexígeno), potencia el efecto orexígeno del Ghrelin. Los niveles basales de esta citokina están elelevados en la AHF e inducen en el hipotálamo, un aumento de la actividad del CRH. Esta hormona, a su vez, inhibe la secreción pulsátil del GnRH. El Ghrelin, además de ser un potente GH secretagogo, influye en la secreción de insulina e interviene en la metabolización de los glúcidos y lípidos. Normalmente se puede observar un ascenso preprandial del Ghrelin, seguido por un descenso posprandial relacionado con la sensación de saciedad. En los obesos, este descenso es menos pronunciado y lento. En cambio, en las mujeres anoréxicas la caída de este orexígeno es más rápida. Ambos comportamientos resultan ser acciones desfavorables para sus respectivas patologías. La administración de Ghrelin induce un rápido incremento de la glucemia y reducción de los niveles de insulina. Este aumento de la glucemia precede al descenso de la insulina, sugiriendo que el Ghrelin podría estimular directamente la glucogenólisis en el hígado. La hiperghrelemia podría entonces ser considerada como un probable mecanismo defensivo tendiente a prevenir la hipoglucemia de estas pacientes amenorreicas y desnutridas. Por otro lado, la hiperghrelemia basal en la AHF sería un efecto secundario a la resistencia a la insulina, la cual a su vez, es inducida por los niveles elevados de los ácidos grasos provenientes de la lipólisis que se encuentra acentuada en estas pacientes. La correlación negativa entre la insulina y el Ghrelin probablemente es mediada por el sistema vagal, como lo sugiere el aumento del polipéptido pancreático, un marcador confiable de la actividad vagal. Adicionalmente, el hipercortisolismo de estas pacientes y posiblemente la somatostatina a través de sus receptores en el páncreas, podrían regular en forma negativa la actividad de los receptores de insulina, con el consiguiente incremento del Ghrelin. Conclusión: el ascenso del Ghrelin en la AHF y sus particulares interrelaciones con la insulina y el eje adrenal convergen para mantener el equilibrio homeostático, intentando facilitar así el aporte de metabolitos energéticos a estas pacientes desnutridas, frecuentemente osteosporóticas, inmunodeprimidas y con un alto riesgo cardiovascular.

OBJECTIVE: To describe a comprehensive approach to women with severe Asherman syndrome and amenorrhea, including preoperative, operative, and postoperative care and subsequent resumption menses, and pregnancy. DESIGN: Retrospective case series. SETTING: Tertiary care teaching hospital. PATIENT(S): Twelve women with severe Asherman syndrome and amenorrhea. INTERVENTION(S): Preoperative administration of prolonged preoperative and postoperative oral E(2) to enhance endometrial proliferation, intraoperative abdominal ultrasound-directed hysteroscopic lysis of uterine synechia to ensure that the dissection is performed in the proper tissue plane, placement of a triangular uterine balloon catheter during surgery, and postoperative removal with placement of a copper intrauterine device (IUD) to maintain separation of the cavity and mechanically lyse newly formed adhesions during removal. MAIN OUTCOME MEASURE(S): Resumption of menses, pregnancy, and delivery. RESULT(S): All women resumed menses, although 5 of 12 had a preoperative maximal endometrial thickness of 4 mm or less, with follow-up ranging from 6 months to 10 years. Six of nine women less than age 39 years (67%) became pregnant, and four of six achieved a term or near-term delivery. CONCLUSION(S): Comprehensive management provides the best possible outcomes in poor-prognosis women with severe Asherman syndrome.

OBJECTIVE: We conducted this meta-analysis of published data to assess the exact prognostic value of adjuvant chemotherapy-induced amenorrhea (CIA) as a prognostic factor for premenopausal breast cancer. METHODS: We searched for all relevant studies published before May 2014 in the PubMed, OVID, and EMBASE databases. Relative risks (RRs) were used to estimate the association between CIA and various survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: This meta-analysis identified 13 eligible studies including 5,513 cases and 2,008 controls for DFS and 5 eligible studies including 2,331 cases and 776 controls for OS. Results demonstrated that CIA is associated with improved DFS (RR, 0.67; 95% CI, 0.61-0.74; P < 0.001) and OS (RR, 0.60; 95% CI, 0.50-0.72; P < 0.001). In subgroup analyses, CIA was found to affect DFS (RR, 0.73; 95% CI, 0.61-0.88; P = 0.001) in estrogen receptor (ER)-positive patients; however, similar results were not observed in ER-negative patients (for DFS: RR, 0.97; 95% CI, 0.66-1.41; P = 0.858). Participants with CIA achieved a significantly better prognosis than participants without CIA, irrespective of nodal status, chemotherapy regimen, endocrine therapy, or publication year. CONCLUSIONS: This meta-analysis clarifies that CIA contributes to improved prognosis in premenopausal women with ER-positive breast cancer and is at least partially responsible for the benefits of adjuvant chemotherapy in these women, which induce chemical castration.

To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its therapeutic impact in premenopausal breast cancer patients. A systematic search was performed to identify clinical studies that compared the incidence of CIA with different chemotherapy regimens and oncological outcomes with and without CIA. The fixed-effects and random-effects models were used to assess the pooled estimates. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. A total of 15,916 premenopausal breast cancer patients from 46 studies were included. The cyclophosphamide-based regimens, taxane-based regimens, and anthracycline/epirubicin-based regimens all increased the incidence of CIA with pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11-1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and taxanes (CAT/CET) caused the highest rate of CIA compared with the other three drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with CIA were found to exhibit better disease-free survival (DFS) and overall survival (OS) compared with patients without CIA. With respect to molecular subtype, this DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 % CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all contributed to elevated rates of CIA, and CIA was not merely a side effect of chemotherapy but was a better prognostic marker, particularly for ER-positive premenopausal early-stage breast cancer patients. However, this topic merits further randomized control studies to detect the associations between CIA and patient prognosis after adjusting for age, ER status, and other influential factors.

OBJECTIVE: To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. DESIGN: From January 2000 to August 2006, 326 premenopausal women (<or=50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, woman's age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. RESULTS: The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group 1 (less than 40 years old) and 198 women in group 2 (age >or=40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. CONCLUSIONS: This study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea or resumption of menstruation and contraceptive options.

A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for contraception and who had experienced at least 6 months of drug induced amenorrhea, were randomized to either switching their method of contraception to Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem users had experienced some vaginal bleeding, compared with 10% of DMPA users. Time to resumption of vaginal bleeding was related to the duration of DMPA use to the duration of DMPA induced amenorrhea, and to the body mass index of the user. Over the 6 months of follow-up, 94% of Cyclofem users complained of some side effects, compared with 22% of DMPA users. The most frequently cited problems among Cyclofem users included breast tenderness, abdominal pain, and dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of the study. It is concluded that switching to Cyclofem is a new option for DMPA users who are concerned about amenorrhea. Although using Cyclofem in this setting will not meet the needs of all such women, its effectiveness in inducing vaginal bleeding justifies a trial in those who have no contraindication to estrogen treatment.