Evaluación de tecnología sanitaria: anovulatorios orales combinados congestodeno comparados con los combinados con levonorgestre / Health technology assessment: combined oral contraceptives containing gestodene compared with those containing levonorgestrel

Esta evaluación de tecnología sanitaria compara un nuevo anovulatorio oral combinado con etinil estradiol 20µ más gestodeno 75µ, con el que contiene etinil estradiol 30µ más levonorgestrel 150µ, utilizado hasta ahora en el subsistema de salud pública de la provincia de Neuquén. De acuerdo a las evidencias halladas, en cuanto a equivalencia de eficacia y riesgos de seguridad –principalmente relativas al aumento significativo en el riesgo de presentar trombosis venosa y embolia pulmonar– se recomienda fuertementeno incorporarlo al vademécum provincial.

PI3K, AKT, and P-AKT levels in thin endometrium.

The aim of this study was to explore the expression of PI3K, AKT, and P-AKT, and to investigate the role of PI3K/AKT signaling pathway in thin endometrium. We included 40 women treated in affiliated Shenzhen Nanshan People's Hospital of Guangdong Medical University for endometrial conditions between August 2013 and January 2015, 20 with a normal endometrium, and 20 with thin endometrium. The expression of PI3K, AKT, and P-AKT was evaluated by the immunohistochemical S-P method. The expression of PI3K, AKT, and P-AKT proteins was significantly lower in the thin endometrium group than in the normal endometrium group (P < 0.05). The expression of PI3K and AKT was positively correlated with the expression of P-AKT. The expression of PI3K, AKT, and P-AKT proteins in the thin endometrium decreases during the proliferative phase, and this process could be associated with PI3K/AKT signaling.

Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P < 0.0001, and P < 0.0001, respectively). The percentage of sperm with progressive motility was lower after incubation with vaginal mucus collected from estrous ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P < 0.0001, respectively). The sample incubated for 30 minutes with mucus from ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P < 0.0001). The percentage of sperm with functional membrane was significantly lower in the sample incubated for 30 minutes with vaginal mucus from ewes treated with IS than in the other three treatments (P < 0.0001). After 90 minutes, the percentage was still lower than that in the sample collected from ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P < 0.0001 and P = 0.008, respectively). The percentage of apoptotic spermatozoa was greater in samples incubated during 30 minutes with vaginal mucus collected from ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS.

Retiro temprano del implante subdérmico con etonogestrel en usuarias de un programa de anticoncepción de Tunja - Boyacá, Colombia / Early removal of subdermal implant containing Etonogestrel in users of a contraceptive program from Tunja - Boyacá, Colombia

Introducción: Los implantes subdérmicos proveen alta efectividad anticonceptiva reversible; no obstante, con su empleo ocurren algunos efectos colaterales. Se ha demostrado que algunas mujeres son menos tolerantes a ellos y solicitan tempranamente el retiro. Objetivo: Evaluar factores relacionados con el retiro del implante subdérmico Implanon®, en mujeres usuarias del programa ambulatorio de Planificación Familiar de una institución de Salud ubicada en Tunja. Materiales y métodos: Estudio observacional, de corte transversal analítico. Se revisaron las historias clínicas de 184 usuarias que solicitaron el retiro del implante en el período comprendido entre 2009 y 2012; se registraron las razones aducidas por las pacientes para solicitar el retiro del implante subdérmico, excluyendo el deseo de una nueva gestación y el tiempo de empleo. Resultados: La media de edad fue de 27,8 años; el tiempo mínimo de uso fue 2 meses, con media de 2,7 años (SD=1,7), la principal razón fue cambios en el patrón de sangrado genital (74,5%), seguida de cefalea (71,7%), cambios en el estado de ánimo (57,6%), dolor pélvico 57,1% y dolor de origen venoso 42,9%; la mayoría de efectos se presentan al inicio de la inserción y tienden a desaparecer en el curso de los primeros meses, con excepción de la cefalea y los cambios de peso. Conclusiones: El implante subdérmico es un método anticonceptivo altamente eficaz; es recomendable realizar intervenciones de educación en salud previo a la inserción.

Introduction: Subdermal implants provide high reversible contraceptive effectiveness; however, some side effects occur with their use. It has been shown that some women are less tolerant to them so they ask for an early retirement. Objective: To assess factors related to the removal of the subdermal implant Implanon ® in women who are users of the ambulatory family planning program of a health institution located in Tunja. Materials and methods: An observational, analytical cross-sectional study was made where the medical histories of 184 users who requested the removal of the implant between 2009 and 2012 were reviewed. The reasons given by patients to request the removal of the subdermal implant were registered, excluding the desire for a new pregnancy and the time use. Results: It was found that the average age was of 27,8 years; the minimum time of use was 2 months with average of 2.7 years (SD = 1, 7). The main reason to request the procedure was due to the changes in their period (74.5%), followed by headache (71.7%), changes in mood (57.6%), pelvic pain (57.1%) and pain of venous origin (42.9%). Most effects occur at the beginning of the inclusion and tend to disappear in the course of the first months, except for the headache and weight changes. Conclusions: The subdermal implant is a highly effective method of birth control. It is recommended to make effective health education interventions prior to insertion.

Bimodal binding and free energy of the progesterone receptor in the induction of female sexual receptivity by progesterone and synthetic progestins.

Synthetic progestins (SPs) are used for regulation of fertility, contraception and hormone replacement therapy. The acetylated medroxyprogesterone (MPA), megestrol (MGA) and chlormadinone (CLA) are related to progesterone (P). Other SPs are 19-nortestosterone derivatives such as: norethisterone (NET), norethynodrel (NED) or the 13-ethyl gonane, levonorgestrel (LNG). We studied MPA, NET, NED and LNG in a dose-response manner to induce sexual receptivity in rats. Results showed that MPA, NET and NED act as partial agonists, with similar or lower potency than P. However, LNG is a full agonist. Additionally, the molecules of MPA, MGA, CLA, NET, NED, LNG, and P, were submitted to computer calculations at ab initio quantum mechanics theory, to obtain their electronic structure and molecular properties. The aim was to correlate their behavioral effect with their physicochemical properties. In addition, the crystals of P, NET and LNG bound to the progesterone receptor (PR) were studied. The PR crystallizes as a dimer forming two monomers (mA and mB), in which Gln725 interacts in either of two possible ways with the C3-carbonyl pharmacophore of progestins. P binds differentially to both PR monomers, while NET binds exclusively as mA and LNG binds only as mB in both monomers with no difference. Energetically, binding of LNG and P to mB, is more favorable than that of NET and P to mA. Consequently, this bimodal mechanism increases the action possibilities of SPs on biological systems. Interestingly, progestin potency depends mostly on local molecular structure and electronic features, prevailing over total molecular properties.

Metabolic effects of contraceptive implants in adolescents.

BACKGROUND: This prospective study analyzed the metabolic effects of an etonogestrel implant used for 1 year by adolescents. STUDY DESIGN: The study population comprised 47 postpartum adolescents (mean 17.2 years old) managed at the Family Planning Sector of São Paulo Federal University. Participants received an implant containing etonogestrel (68 mg) within 6 months of delivery (on average 102 days after giving birth) and were followed for 1 year. Blood was collected at baseline and 12 months later to assess total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), hemogram, urea, creatinine, sodium, potassium, fasting glucose, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and bilirubin. RESULTS: Three adolescents did not return after receiving the implant despite telephone messages and a telegram and were excluded from the clinical and final laboratory analyses. All 44 patients completed the 12 months of follow-up, resulting in a study discontinuation rate of 0%. No implants were removed. Laboratory analyses were completed in 37 adolescents. After 1 year of using the implant, there was a significant increase in mean hemoglobin, hematocrit and indirect bilirubin concentrations and of the HDL-C/TC and HDL-C/LDL-C ratios. Additionally, there was a significant decrease in mean TC level as well as LDL-C, very low-density lipoprotein cholesterol, TG, SGOT and SGPT. These results suggest that the etonogestrel implant does not interfere directly with the risk of cardiovascular diseases because it improves the lipid profile. There were no pregnancies during the study. CONCLUSION: Our results indicate that an etonogestrel implant used by adolescents for 1 year is associated with changes in the lipid profile and hepatic function without adverse clinical effects.

Effects of drospirenone/estradiol on steroid receptors and Bcl-2 in the postmenopausal endometrium.

OBJECTIVE: To evaluate the effect of drospirenone with 17ß-estradiol on the histology and expression of estrogen and progesterone receptors and of Bcl-2 protein, in endometrium of postmenopausal women. METHOD: Forty postmenopausal women, including controls, participated in this study evaluating oral hormone replacement treatment combining 2 mg/day of drospirenone with 1 mg/day of 17ß-estradiol administered for a 24-week period. The effect on the endometrium was assessed by histology and the apoptosis marker Bcl-2. The immunoexpression of estrogen (ER) and progesterone (PR) receptors in the endometrium was also measured. RESULTS: No increase in endometrial thickness was evident after either treatment, although endometrial histology was atrophic in most biopsies. The drospirenone/estradiol group showed higher expression of ER and PR in glandular epithelium compared to stroma, but the Bcl-2 protein was more immunoreactive in stroma than in glandular epithelium. Compared to controls, drospirenone/estradiol users showed higher immunoexpression of ER, PR and Bcl-2 in both glandular epithelium and endometrial stroma. CONCLUSION: A 24-week course of drospirenone with 17ß-estradiol resulted in low proliferation and was shown to lead to atrophic endometrium. The novel progestogen drospirenone seems to have favorable effects on the endometrium of postmenopausal women due to its pro-apoptotic action in glandular epithelium.

Induction of ovarian follicular wave emergence and ovulation in progestin-based timed artificial insemination protocols for Bos indicus cattle.

The present study aimed to evaluate the efficacy of different inducers of new follicular wave emergence (FWE) and ovulation in fixed-time artificial insemination (FTAI) synchronization protocols using norgestomet ear implants (NORG) in Bos indicus cattle. In Experiment 1, the synchronization of FWE was evaluated when two different estradiol esters in different doses [2mg estradiol benzoate (EB), 2.5mg EV or 5mg estradiol valerate (EV)] were administered with NORG implant insertion in B. indicus cattle (estrous cyclic heifers and cows with suckling calves; n=10 per treatment). After estradiol treatment, ovarian ultrasonic exams were performed once daily to detect the interval between treatment and FWE. There were significant treatment-by-animal category interaction (P=0.05) on the interval from the estradiol treatment to FWE. An earlier (P<0.0001) and less variable (P=0.02) interval from estradiol treatment to FWE was observed in heifers treated with EB (2.5±0.2; mean±SE) than in those treated with 2.5mg EV (4.2±0.3) or 5mg EV (6.1±0.6). Cows treated with 5mg EV (4.0±0.5) had longer (P=0.05) interval than cows receiving EB (2.5±0.2), however, there was an intermediate interval in those cows treated with 2.5mg EV (3.1±0.4). In Experiment 2, the number of uses of the NORG implant (new; n=305 or previously used once; n=314) and three different ovulation induction hormones [0.5mg estradiol cypionate (EC) at implant removal (n=205), 1mg EB given 24h after implant removal (n=219), or 100µg gonadorelin (GnRH) given at FTAI (n=195)] were evaluated in Nelore heifers (2×3 factorial design). Similar pregnancy per AI (P/AI; 30 days after FTAI; P>0.05) were achieved using each of the three ovulation induction hormones (EB=40.6%; EC=48.3%, or GnRH=48.7%) and with a new (47.2%) or once-used NORG implant (44.3%). In Experiment 3, the effect of different ovulation induction hormones for FTAI [1mg EC at NORG implant removal (n=228), 10µg buserelin acetate at FTAI (GnRH; n=212) or both treatments (EC+GnRH; n=215)] on P/AI was evaluated in suckled beef cows treated with a once-used NORG implant and EB to synchronize the FWE. Similar P/AI (P=0.71) were obtained using GnRH (50.9%), EC (51.8%) or both treatments (54.9%) as ovulation induction hormones. Therefore, both doses of EV (2.5 or 5.0mg) with NORG implant delayed and increased the variation of the day of new FWE compared with EB in B. indicus cattle. These effects were more pronounced in B. indicus heifers than cows. Synchronization protocols for FTAI with either a new or once-used NORG implant with EB at insertion to induce a new FWE and either the use of EB, EC or GnRH as ovulation induction hormones may be successful in B. indicus heifers. Also, when a once-used NORG implant was used, either the administration of EC, GnRH or both as ovulation inducers resulted in similar P/AI in suckled B. indicus cows, showing no additive effect of the combination of both ovulation induction hormones.

Níveis séricos de progesterona em vacas ovariectomizadas tratadas com Mad4® com diferentes concentrações e vias de administração / Serum progesterone levels in ovariectomised cows treated with mad-4® with different concentrations and routes of administration

Background: Progesterone and synthetic progestogens are used to prepare the uterus for pregnancy, and for the hypothalamus, pituitary and ovaries to respond to endogenous and exogenous gonadotropins. The object of this work was to check serum progesterone concentrations in ovariectomised cows, to determine pharmacokinetics of MAD-4 ® product. Materials, Methods & Results: A group of eigth Braford cows was divided into two groups, in two experiments. In experiment I, both groups received 250 mg of progesterone by different routes of application: intramuscular or subcutaneous. In experiment II, subcutaneous application was used in both groups, the differentiation of the treatments lying in the concentration of progesterone: treatment 2 received 250 mg progesterone and treatment 3 was administered 375 mg of progesterone. In the first 24 h samples were collected in intervals of 6 hours, then every 24 h up to 192 h (day 8). In experiment I there was a significant difference (P < 0.05) at 96 h, showing greater concentration in treatment 2 compared to treatment 1 (1.54 ng/mL vs. 0.48 ng/ mL, respectively). In experiment II, in the measures undertaken at 144 h, 168 h and 192 h with significant difference (P < 0.05), concentrations of progesterone in treatment 2 were lower when compared to treatment 3 (0.79 ng/mL vs. 1.63 ng/mL, 0.66 ng/ mL vs. 1.36 ng/mL and 0.49 ng/mL vs. 1.11 ng/mL respectively for hours and treatments). Due to the fact that the types of progestogens and doses used to control the estrous cycle in cattle may be less effective than endogenous progesterone (a corpus luteum) with respect to suppression of LH, the high frequency of LH pulses results in development of “persistent” follicles containing aged eggs of low fertility. In this study, the application of 250 mg of intramuscular and subcutaneous long action injectable progesterone elevated progesterone serum concentration above 1 ng/mL. Subcutaneous application presented levels exceeding 1 ng/mL for a longer time, from 6 to 96 h. This treatment probably suppresses LH pulses temporarily without staying very long in the bloodstream; for this reason it doesnt impair fertility. The same cannot be said in the treatment situation with the application of 375 mg subcutaneous long-action injectable progesterone, because, as long as progesterone was measured (day 8), the concentration remained higher than 1 ng/mL. Discussion: Vaginal silicone implants impregnated with 0.5 g of progesterone, when used for the second time (7 days each time), failed to maintain serum progesterone levels for more than 24 h higher than 1 ng/mL. In this study, treatment with 250 mg intramuscular long-action injectable progesterone showed similar serum concentrations over time, because between 24 and 48 h the levels were below 1 ng/mL. Parenteral routes of administration include, among others, the intramuscular (IM) and subcutaneous (SC). The intramuscular route is characterised by a relatively rapid absorption via the subcutaneous, is characterized by a slower absorption and continuous. Treatment of ovariectomised cows with long-acting injectable progesterone in different doses and by different routes resulted in significantly different serum concentrations at some moments, characteristic of each route of administration and doses used. In this study we can conclude that the seemingly more appropriate treatment is that which makes use of 250 mg of long-acting progesterone, subcutaneously injected, keeping progesterone serum levels higher than 1ng/mL per period of four days.(AU)

Níveis séricos de progesterona em vacas ovariectomizadas tratadas com Mad4® com diferentes concentrações e vias de administração / Serum progesterone levels in ovariectomised cows treated with mad-4® with different concentrations and routes of administration

Background: Progesterone and synthetic progestogens are used to prepare the uterus for pregnancy, and for the hypothalamus, pituitary and ovaries to respond to endogenous and exogenous gonadotropins. The object of this work was to check serum progesterone concentrations in ovariectomised cows, to determine pharmacokinetics of MAD-4 ® product. Materials, Methods & Results: A group of eigth Braford cows was divided into two groups, in two experiments. In experiment I, both groups received 250 mg of progesterone by different routes of application: intramuscular or subcutaneous. In experiment II, subcutaneous application was used in both groups, the differentiation of the treatments lying in the concentration of progesterone: treatment 2 received 250 mg progesterone and treatment 3 was administered 375 mg of progesterone. In the first 24 h samples were collected in intervals of 6 hours, then every 24 h up to 192 h (day 8). In experiment I there was a significant difference (P < 0.05) at 96 h, showing greater concentration in treatment 2 compared to treatment 1 (1.54 ng/mL vs. 0.48 ng/ mL, respectively). In experiment II, in the measures undertaken at 144 h, 168 h and 192 h with significant difference (P < 0.05), concentrations of progesterone in treatment 2 were lower when compared to treatment 3 (0.79 ng/mL vs. 1.63 ng/mL, 0.66 ng/ mL vs. 1.36 ng/mL and 0.49 ng/mL vs. 1.11 ng/mL respectively for hours and treatments). Due to the fact that the types of progestogens and doses used to control the estrous cycle in cattle may be less effective than endogenous progesterone (a corpus luteum) with respect to suppression of LH, the high frequency of LH pulses results in development of “persistent” follicles containing aged eggs of low fertility. In this study, the application of 250 mg of intramuscular and subcutaneous long action injectable progesterone elevated progesterone serum concentration above 1 ng/mL. Subcutaneous application presented levels exceeding 1 ng/mL for a longer time, from 6 to 96 h. This treatment probably suppresses LH pulses temporarily without staying very long in the bloodstream; for this reason it doesn’t impair fertility. The same cannot be said in the treatment situation with the application of 375 mg subcutaneous long-action injectable progesterone, because, as long as progesterone was measured (day 8), the concentration remained higher than 1 ng/mL. Discussion: Vaginal silicone implants impregnated with 0.5 g of progesterone, when used for the second time (7 days each time), failed to maintain serum progesterone levels for more than 24 h higher than 1 ng/mL. In this study, treatment with 250 mg intramuscular long-action injectable progesterone showed similar serum concentrations over time, because between 24 and 48 h the levels were below 1 ng/mL. Parenteral routes of administration include, among others, the intramuscular (IM) and subcutaneous (SC). The intramuscular route is characterised by a relatively rapid absorption via the subcutaneous, is characterized by a slower absorption and continuous. Treatment of ovariectomised cows with long-acting injectable progesterone in different doses and by different routes resulted in significantly different serum concentrations at some moments, characteristic of each route of administration and doses used. In this study we can conclude that the seemingly more appropriate treatment is that which makes use of 250 mg of long-acting progesterone, subcutaneously injected, keeping progesterone serum levels higher than 1ng/mL per period of four days.

Safety of contraceptive method use among women with systemic lupus erythematosus: a systematic review.

OBJECTIVE: To evaluate the evidence on the safety of contraceptive method use among women with systemic lupus erythematosus (SLE). DATA SOURCES: We searched the PubMed, MEDLINE, and LILACS databases for peer-reviewed articles published from database inception through January 2009, concerning the safety of contraceptive use among women with SLE. METHODS OF STUDY SELECTION: We included studies that examined health outcomes among women using a contraceptive method after the diagnosis of SLE. The quality of each individual piece of evidence was assessed using the U.S. Preventive Services Task Force grading system. TABULATION, INTEGRATION, AND RESULTS: Our search yielded 275 articles. A total of 14 articles that reported on 13 studies met our inclusion criteria. Available evidence, including two good-quality randomized controlled trials, indicates that use of combined oral contraceptives does not lead to increased flares of disease or worsening disease activity in women with inactive or stable active SLE. No increase in disease activity with use of progestogen-only contraceptives was noted in four studies. Limited evidence indicates a possible increased risk of thrombosis in women with positive antiphospholipid antibodies and history of oral contraceptive use. Limited evidence indicates that the use of the copper intrauterine device is not associated with worsening disease activity or infection in women with SLE. CONCLUSION: Available evidence indicates that many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives. The benefits of contraception for many women with SLE likely outweigh the risks of unintended pregnancy in this population. Women with positive antiphospholipid antibodies are not good candidates for combined hormonal contraception given their elevated baseline risk of thrombosis.

Treatment with an intravaginal progestagen and estradiol to prevent prolonged anestrus in crossbred zebu cows under tropical conditions.

To study the effectiveness of a treatment with an intravaginal progestagen in combination with estradiol-17beta (E-17beta) on estrus induction, prevention of prolonged anestrus and fertility in noncycling crossbred zebu cows, a trial was conducted in a farm in Zulia state, Venezuela. Fifty noncycling suckled crossbred cows (B. taurus x B. indicus) with 60 dpp were randomly allotted to one of the following treatments: MAP+E-17beta (n=22), intravaginal device (250 mg of MAP) during 7 days + 50 mg of MAP and 5 mg of E-17beta im (day 0) and 1.5 mg of E-17beta im (day 8) (Pregnaheat-E; VIATECA-Venezuela); CG (n=28), control group without hormonal treatment. The MAP+E-17beta group showed higher (P<0.05) estrus and synchronization rates (59.1 and 36.4 %) than CG (25.0 and 3.5 %). Cows receiving MAP had higher (P<0.05) overall pregnancy rate than CG (45.5 and 17.8 %, respectively). A decreased (P<0.05) anestrus rate was observed in MAP+E-17beta (31.8%) compared to CG (57.1%). Calving-conception interval was shorter (P<0.05) in MAP+E-17beta (132.5+/-16.8 days) than in CG (178.9+/-14.7 days). In conclusion, treatment with MAP+E-17beta at 60 days postpartum was effective to induce estrus, prevent prolonged anestrus, and reduce the calving-conception interval, improving reproductive performance in dual purpose crossbred Zebu cows.

Levonorgestrel antagonism on estrogen-induced pituitary tumors is mediated by progesterone receptors.

Using both IN VITRO and IN VIVO approaches, we studied the antagonism exerted by the synthetic progestin levonorgestrel on estrogen-induced prolactinomas, considering that levonorgestrel shows partial androgenic properties and that androgens inhibit estrogen-induced prolactin synthesis and secretion. In the tumors, binding of estrogens to their receptors was competed neither by progesterone receptor ligands nor by androgen receptor ligands, ruling out direct inhibitory effects of these drugs on tumor development. Progestin binding was competed by the progesterone receptor agonists progesterone and levonorgestrel, by the antagonist mifepristone, and also by the androgen dihydrotestosterone, whereas the androgen receptor antagonist hydroxyflutamide was a weak competitor. In addition, both progesterone receptor and androgen receptor ligands competed for binding to androgen receptors. In primary cultures of pituitary tumors, levonorgestrel decreased prolactin secretion, an effect that was blocked by mifepristone but not by hydroxyflutamide. IN VIVO results indicated that levonorgestrel inhibition of both estrogen-induced pituitary weight increment and hyperprolactinemia was reduced by mifepristone, whereas flutamide was unable to block levonorgestrel effects. Our results suggest that even when an interaction of levonorgestrel with androgen receptors in the tumors is possible, the antagonistic effects of levonorgestrel on tumor development and functionality are mediated by progesterone receptors.

Follicle deviation and ovulatory capacity in Bos indicus heifers.

The objectives of Experiment 1 were to determine the interval from ovulation to deviation, and diameter of the dominant follicle (DF) and largest subordinate follicle (SF) at deviation in Nelore (Bos indicus) heifers by two methods (observed and calculated). Heifers (n = 12) were examined ultrasonographically every 12 h from ovulation (Day 0) to Day 5. The time of deviation and diameter of the DF and largest SF at deviation did not differ (P>0.05) between observed and calculated methods. Overall, deviation occurred 2.5+/-0.2 d (mean +/- S.E.M.) after ovulation, and diameters for DF and largest SF at deviation were 6.2+/-0.2 and 5.9 +/- 0.2 mm, respectively. Experiment 2 was designed to determine the size at which the DF acquires ovulatory capacity in B. indicus heifers. Twenty-nine heifers were monitored every 24 h by ultrasonography, from ovulation until the DF reached diameters of 7.0-8.4 mm (n=9), 8.5-10.0 mm (n=10), or >10.0 mm (n=10). At that time, heifers were treated with 25 mg of pLH and monitored by ultrasonography every 12 h for 48 h. Ovulation occurred in 3 of 9, 8 of 10, and 9 of 10 heifers, respectively (P<0.05). In summary, there was no significant difference between observed and calculated methods of determining the beginning of follicle deviation. Deviation occurred 2.5 d after ovulation when the DF reached 6.2 mm, and ovulatory capacity was acquired by DF as small as 7.0 mm.

Assessment of the intensity of behavioural traits and ovulation between synchronized and non-synchronized cows.

Thirty cyclic, non-suckled Brahman cows were divided into three groups, all of which were synchronized sequentially with CIDR-B and observed continuously for 100 h to determine different behavioural oestrus signs. Twenty-four hours after implant withdrawal, all synchronized cows in the group, together with all other cows displaying oestrus, were subjected to intensive ultrasonographic observations (every 6 h for 120 h) to pinpoint the moment of ovulation. In the first group, oestrus and ovulation response was 60% (6/10), in the second 44% (4/9) showed oestrus and six ovulated, and in the third group oestrus and ovulation were 80% (8/10). Significant differences were observed between the second and third groups (p < 0.05). No differences were observed in the duration of oestrus, time when oestrus was displayed after implant withdrawal, time of ovulation and onset of oestrus, end of oestrus to ovulation, and intensity of oestrus on a point scale. The relationship between duration of oestrus and time of ovulation was r(2) = 0.16. Ovulation, on average, was 32.1 +/- 14.5 h after the onset of oestrus, 22.3 +/- 16.5 h after the end of oestrus, and 91.8 +/- 16.7 after implant withdrawal, although no significant differences were observed. One non-synchronized animal showed oestrous activity in the second group but failed to ovulate. In the third group, 8 animals showed oestrus, 4 with high concentrations of progesterone. Of the other four one ovulated. In conclusion, oestrous behaviour is not necessarily the best marker to predict the time when ovulation takes place due to variation in the length of the oestrous period and the possible integration of non-ovulatory animals into sexually active groups.

The effects of synthetic 19-norprogestins on osteoblastic cell function are mediated by their non-phenolic reduced metabolites.

The key role of estrogens on osteoblastic cell function is well documented; however, the role of progesterone (P) and synthetic progestins remains controversial. While several reports indicate that P has no significant effects on bone cells, a number of clinical studies have shown that 19-norprogestins restore postmenopausal bone loss. The mechanisms by which 19-norprogestins induce estrogen-like effects on bone cells are not fully understood. To assess whether the actions of 19-norprogestins on osteoblasts are mediated by their non-phenolic metabolites, we studied the effects of norethisterone (NET), levonorgestrel (LNG), and two of their A-ring reduced derivatives upon cell proliferation and differentiation in neonatal rat osteoblasts. Osteoblast function was assessed by determining cell DNA, cell-associated osteocalcin and calcium content, alkaline phosphatase activity, and mineral deposition. P failed to induce changes on osteoblasts, while NET and LNG exerted a number of actions. The most striking finding was that the 3beta,5alpha- and 3alpha,5alpha-tetrahydro derivatives of NET and LNG induced osteoblast proliferation and differentiation with higher potency than those exerted by their parent compounds, mimicking the effects of estradiol. Interestingly, osteoblast differentiation and mineral deposition induced by NET and LNG were abolished by finasteride, a 5alpha-reductases inhibitor, while the potent effect on osteoblast proliferation induced by progestin derivatives was abolished by a steroidal antiestrogen. Results demonstrate that A-ring reduced derivatives of NET and LNG exhibit intrinsic estrogen-like potency on rat osteoblasts, offering a plausible explanation for the mechanism of action of 19-norprogestins in bone restoration in postmenopausal women and providing new insights for hormone replacement therapy research.

Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women.

OBJECTIVE: This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women. PATIENTS AND METHODS: A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence. RESULTS: In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively). CONCLUSIONS: Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women.

Reproductive response in suckling Corriedale ewes to the ram effect during the non-breeding season: effect of postpartum condition and the use of medroxyprogesterone priming.

The response to the ram effect and the use of progestagen priming was studied in postpartum suckling Corriedale ewes. Two experiments were carried out during the non-breeding season. In experiment 1, the effectiveness of the ram effect to induce fertile oestrus in postpartum ewes was determined. While no significant differences in the frequency of ewes in oestrus were found, the overall conception rate was significantly higher in ewes that were weaned at least 6 months before the study started (63.3%) than in 60-90 days postpartum ewes (45.3%, p < 0.01). In experiment 2, the influence of medroxyprogesterone acetate priming on the response to the ram effect in suckling Corriedale ewes was determined. The frequency of ewes in oestrus and conception rate between ewes that remained unprimed and 6-days-primed ewes were similar. We conclude that it is possible to induce oestrus in postpartum suckling Corriedale ewes using the ram effect during the non-breeding season and that the use of progestagen priming seems to be ineffective in improving the response of postpartum ewes to the ram effect.

Effect of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on tolerance, cycle control, general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception.

PURPOSE: Positive effects on premenstrual symptoms have been observed with low-dose oral contraceptives. Drospirenone is a synthetic progestogen with antiandrogenic and antimineralocorticoid effects. This open-label, multicenter study evaluated the effects of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on safety, cycle control, general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception. MATERIALS AND METHODS: A total of 241 healthy volunteers with symptoms of premenstrual disorder was enrolled in the study. Of the final sample, 203 completed the six-cycle treatment and were included in the efficacy analysis whereas 236 were included in the tolerability analysis. The subjects recruited to the study were required to fill up the Psychological General Well-Being Index (PGWBI). RESULTS: There was no significant change in body weight or blood pressure throughout the treatment. Adverse events reported by patients during treatment consisted of those already known to be associated with oral contraceptive use. PGWBI scores were significantly higher after six cycles of treatment compared with baseline values (p<.0001). A total of 198 (84.2%) subjects reported a great improvement in premenstrual symptoms. CONCLUSIONS: The results of this study confirm that oral use of a combination of ethinylestradiol 30 microg and drospirenone 3 mg provides good cycle control, is well tolerated and has a positive impact on symptoms of premenstrual disorder.

Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year.

PURPOSE: This study was undertaken to evaluate the effects of a subdermal implant containing nomegestrol acetate (Uniplant) on endometrial histology and ovarian function. METHODS: Twenty healthy female volunteers of reproductive age were included and completed a menstrual diary throughout the study. Hysteroscopy, transvaginal sonography and blood sampling were performed prior to implant insertion (control cycle) and following 6 and 12 months of Uniplant use. Transvaginal sonography was performed every other day from Day 8 of the cycle up to the obtainment of sonographic evidence of a 12-mm follicle, then every day until the obtainment of sonographic evidence of follicular rupture and thereafter every other day until the next menstrual bleeding. Blood samples were taken for the measurement of estradiol, follicle-stimulating hormone, luteinizing hormone and progesterone on the same days on which transvaginal sonography was performed. The implants were removed after 1 year. RESULTS: Twenty percent of cycles were ovulatory, and 80% were anovulatory. The development of persistent nonluteinized follicle occurred in 40% of all cycles studied, inadequate luteal phase occurred in 20% of cycles and no follicular development occurred in 40%. Endometrial thickness remained below 8 mm in all cycles studied. Alterations in endometrial vascularization were observed in all treated cycles. CONCLUSION: Our results suggest that this long-acting contraceptive method affects follicular growth and endometrial vascularization, disrupts endometrial architecture and leads to inadequate luteal phase.