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.

Therapeutic options for management of endometrial hyperplasia / 부인종양

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

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.

Effect of the composition and structure of the drug delivery device on the drug release rate / 生物医学工程学杂志

To investigate the effects of the property of drugs and the structure of drug delivery devices on the drug release rate, the effects of sealing methods, length, thickness and drug-loading manner of the silicone tubes on the drug release rate were examined using progestin, testosterone, estradiol as the delivery drugs. The results showed that the property of the drug was the crucial factor to the drug release rate. The sealing methods, length, thickness and drug status of the silicone tubes had significant effects on the drug release rate and the effects were closely related to the property of the drugs. In addition, our newly developed glass-silicone tube has larger drug deposition capability and smaller drug release area, offers an effective and convenient method for the sustained drug delivery with quick release traits in vivo.

A double blind randomized control trial, comparing effect of drospirenone and gestodene to sexual desire and libido.

BACKGROUND: Oral contraceptive is the most commonly used method of fertility control. Yasmin is a combination of a novel progestogen with anti-androgenic and anti-mineralcorticoid activities (3 mg Drospirenone (DRSP) and 30 microg ethinylestradiol (EE)). It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive, lacking undesired effects as with other oral contraceptives such as weight gain. However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE: Investigate the effects of Yasmin on sexual desire, libido and changes in the free androgen index (FAI) compare to Meliane (75 microg gestodene + 20 microg ethinylestradiol). MATERIAL AND METHOD: The authors' report the results of a double blind randomized controlled study using a translated version of the Female Sexual Function Index questionnaire (FSFI) for the assessment of the sexual function. The free androgen index was calculated from measurements of testosterone and sexual hormone binding globulin. RESULT: The result shows statistically significant improvements regarding sexual desire, arousal and overall satisfaction in the Yasmin group. Additionally, an increased frequency of orgasms in the Meliane group was reported. Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free androgen index have not been observed. CONCLUSION: The novel oral contraceptive containing drospirenone (Yasmin) and the non-anti-androgenic progestin containing oral contraceptive (Meliane) do not show unfavorable effects on sexual response and libido.

McCune Albright Syndrome (MCAS): a case series.

McCune Albright Syndrome (MCAS) is an association of, Café-au-lait macules, polyostotic fibrous dysplasia and autonomous hyperfunctioning endocrinopathy. This is a rare disorder seen more commonly in females. We evaluated 7 (6F & 1M) cases under six years of age (4 months to 5.5 yrs) presenting with Café-au-lait spots, polyostotic fibrous dysplasia and/or sexual precocity. All the 7 cases had large Café-au-lait spots, radiologic features of polyostotic fibrous dysplasia were seen in 5 cases. Six girls had precocious puberty with large ovarian follicles and elevated S. Estradiol levels (14-65 pg/dl) with prepubertal gonadotropin levels in 5 of them. Medroxy-progrestrone acetate was used to treat the sexual precocity. Five girls on follow up for 6 months (6mo-16mo) showed cessation of menstrual episodes and regression of ovarian follicles in three, regression in breast size in one, and three girls continued to grow at a height velocity >95th centile for age. Skeletal lesions and skin features did not show any change. No other endocrinopathy was noted. Gonadotropin independent precocious puberty was the only endocrine affection seen in this series.

Some problems of postmenopausal osteoporosis prevention with hormone replacement therapy / 中国医学科学院学报

Estrogen deficiency is the one of pathogenetic causes of postmenopausal osteoporosis. Exogenous estrogen may prevent postmenopausal bone loss, so to prevent postmenopausal osteoporosis and osteoporotic fracture. The effect of estrogen on postmenopausal syndrome can not be substituted with other medicine. However, the attention should be paid to the safety of hormone replacement therapy (HRT) during its long term use, and HRT should be used individually.

Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the reversal effect of nomegestrol acetate (NOM) on mutidrug resistance (MDR) in MCF7/ADR and its mechanism.</p><p><b>METHODS</b>Using tetrazolium dye assay, effects of various concentrations of NOM on sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related genes MDR1, glutathoine S-transferase Pi (GSTpi), Topoisomerase II alpha (Topo II alpha) and MDR related protein (MRP) were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assay. Using flow cytometry (FCM), intracellular ADR concentration effects on cell cycle were observed.</p><p><b>RESULTS</b>NOM significantly reversed MDR in MCF7/ADR. After NOM 20, 10 and 5 micromol/L treatment, the chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal activity of NOM was stronger than that of the precursor compound megestrol acetate, and was comparable to that of verapamail. After treatment with NOM 5 micromol/L both MDR1 and GSTpi mRNA genes expression began to decline on D2 (P < 0.05, & P < 0.01) and reached the lowest level on D3 (both P < 0.01), but the expression levels began to rise on D6 again (both P < 0.05). The expression of MRP and Topo II alpha gave no significant change. Changes of P-gp and GSTpi protein expressions were similar to those of their mRNA expressions, showing early decline and late rise. Two hours after NOM 20, 10, and 5 micromol/L treatment, intracellular ADR concentration increased 2.7, 2.3 and 1.5 times, respectively. FCM data showed that after forty-eight hours, combined administration of NOM (20 micromol/L) and ADR (from low concentration to high concentration), MCF7/ADR cells showed gradual arrest in the G(2)M phase with the increase of ADR dose.</p><p><b>CONCLUSION</b>NOM has strong reversal effects on MDR in MCF7/ADR. The reversal takes place via different routes, i.e. down regulating mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration, and enhancing the arrest of ADR in cells at G(2)M phase.</p>

Comparison of norgestrel- versus cyproterone acetate-containing hormone replacement therapy on lipid-lipoprotein metabolism.

To compare the effects on the lipid profile of estradiol valerate with norgestrel to a regimen of estradiol valerate with cyproterone acetate. Sixty-four healthy women in their perimenopause or early postmenopause, aged between 40-55 years, were randomized to one of the two 21-day sequential regimens: estradiol valerate 2 mg/day for 21 days and combined with either norgestrel 0.5 mg/day or cyproterone acetate 1 mg/day from day 12 to 21, with 7 days of drug-free interval, for 12 cycles. Lipid profiles were followed at baseline, 6 and 12 cycles. Sixty-one subjects completed the study, 30 in the norgestrel group and 31 in the cyproterone group. During 12 cycles of study, serum HDL cholesterol levels decreased significantly in the norgestrel group (p < 0.01) and were unchanged in the cyproterone group. The levels were significantly lower in the norgestrel group than in the cyproterone group (p < 0.05). No differences were found between groups as regards LDL cholesterol and total cholesterol levels. Triglyceride levels decreased significantly in the norgestrel group (p < 0.01), remained unchanged in the cyproterone group and the levels were significantly different between groups (p < 0.01). In conclusion, the study demonstrated that sequential regimen of estradiol valerate with norgestrel produced less favorable HDL cholesterol but more favorable triglyceride levels than the regimen of estradiol valerate with cyproterone acetate.

Uterine blood flow response to hormonal replacement therapy in asymptomatic postmenopausal women: a transvaginal Doppler study.

To evaluate the effect of continuous hormonal replacement therapy (HRT) on Doppler parameters of uterine blood flow in asymptomatic postmenopausal women. Thirty-eight asymptomatic postmenopausal women were recruited into the study from the outpatient menopause clinic, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University. The study population was divided into 20 cases without any HRT (group 1) and 18 cases using continuous conjugated equine estrogen 0.625 mg/day combined with medroxyprogesterone acetate 2.5 mg/day (group 2). The duration of HRT was 21.3 +/- 9.5 (13-56) months. A transvaginal colour flow imaging system (ALOKA SSD-2000 MultiView, Tokyo, Japan) was used to assess uterine blood flow. Quantitative data from areas of colour were evaluated by pulsed Doppler spectrum analysis. Resistance indices (RI) were measured as indicators of uterine perfusion. Both groups were statistically similar with respect to age, parity, age at menopause, height and weight. The endometrial thickness in group 1 and 2 were 3.8 +/- 0.8 and 4.1 +/- 0.6 millimetres, respectively. The left uterine artery RIs of group 1 and 2 were 0.86 +/- 0.08 and 0.84 +/- 0.07, respectively (p = 0.33). The right uterine artery RIs of group 1 and 2 were 0.87 +/- 0.07 and 0.83 +/- 0.06, respectively (p = 0.06). In conclusion, continuous HRT had a non-significant influence on uterine blood flow in the postmenopausal women.

Clinical effects of 17 beta-estradiol and norethisterone acetate in postmenopausal Thai women.

OBJECTIVE: To compare the climacteric symptoms, the bleeding patterns, side effects, endometrial thickness, serum follicular stimulating hormone (FSH) and estradiol level in postmenopause Thai women who received this drug and placebo. STUDY DESIGN: Double blind, randomized placebo controlled trial. MATERIAL AND METHOD: Sixty postmenopausal women attending the menopause clinic at Chulalongkorn Hospital from July, 1996 to December, 1996, were enrolled in the study. The patients were randomized to receive the placebo or drug (17 beta-estradiol 2 mg and norethisterone acetate 1 mg) continuously. After 12 months, 13 patients in the drug group were switched to have placebo and 13 patients in the placebo were switched to the drug group. Recording of patient characteristics, physical and gynecologic examination, pap smear, breast examination and mammogram, climacteric symptom scores, transvaginal ultrasonography, serum FSH and Estradiol level were performed prior to the study. Physical examinations, breast palpitations, measurement of body weight and blood pressure, climacteric symptom scores and side effects were repeated at 3, 6, 12, 18 months. Gynecologic examination, pap smear, serum FSH and estradiol, transvaginal ultrasonography, were repeated at 12 months. RESULTS: The women in the drug group had fewer climacteric symptoms than baseline after 6 months. The incidence of amenorrhea was 74.0 per cent at 12 months. The incidence of abnormal uterine bleeding (spotting and breakthrough bleeding) was 37.0 per cent at 3 months, 29.6 per cent at 6 months, 25.9 per cent at 12 months and 7.1 per cent at 18 months. The women in the drug group had fewer climacteric symptoms than baseline after 6 months. Breast tenderness was the most common side effect. The endometrial thickness decreased significantly in the drug group. Serum FSH decreased and serum estradiol increased significantly in the drug group. CONCLUSION: This combined regimen was more effective in relieving the climacteric symptoms in women who used the drug than those who used the placebo. There was a high incidence of amennorhoea after 12 months. But there was also a high frequency of abnormal bleeding in the first 3 months of treatment. Counseling on the bleeding pattern and common side effects should be conducted before starting the treatment to increase the compliance. This combined regimen proved to be a useful alternative for postmenopausal Thai women who prefer to avoid cyclic bleeding from sequential therapy.

Pregnancy in premature ovarian failure: a possible role of estrogen plus progesterone treatment.

Premature ovarian failure (POF) is a common occurrence in women during their reproductive years. There is paucity of data on spontaneous ovulation and subsequent pregnancies in such women. In this report, we describe three women with POF, two of whom had spontaneous conceptions and the third resumed spontaneous regular menstrual cycles. All these women had received oestrogen-progesterone tablets for many cycles (ethyl oestradiol 0.05 mg and levonorgestrel 0.25 mg a day, 21 days a month). We speculate about the possibility of elevated gonadotrophins causing down regulation of gonadotrophin receptors and restoration of the sensitivity of the few remaining ovarian follicles by lowering of serum gonadotrophins with oestrogen therapy.

Clinical effects of gestrinone for the treatment of pelvic endometriosis in infertile patients.

The clinical efficacy and side effects of oral gestrinone, 2.5 mg twice weekly, were evaluated in this prospective study involving 22 patients with laparoscopically confirmed endometriosis. All patients came to the hospital with infertility problem. After 6 months of treatment, 81 per cent of patients had amenorrhea. Dysmenorrhea and pelvic pain were reduced from 90.9 per cent to 14.3 per cent and 81.8 per cent to 9.5 per cent respectively. Pelvic tenderness and induration were improved from 55.6 per cent and 50.0 per cent to 15.8 per cent and 10.5 per cent respectively. Androgenic effects such as acne was founded in 18.2 per cent of the patients. Return of fertility was observed in 25 per cent (5 patients) after 30-254 days post treatment. No serious side effect was detected during the treatment. The results suggest that gestrinone may be considered an option for the treatment of endometriosis related infertility.

Subdermal levonorgestrel implant: acceptability and user satisfaction

To evaluate the acceptability and user satisfaction on decision making to use subdermal levonorgestrel implant. A prospective, observational study, conducted in the family planning clinic, Department of Obstetrics and Gynaecology at King Hussein Medical Center. Seventy four acceptors were enrolled during a 6 month recruitment period. Two perspective questionnaires were administered to each acceptor. The first was administered at the time of acceptance and the second was administered after 6 months of method use. The most important reasons to choose the method were length of protection [58%], dissatisfaction with past contraceptive methods [54%] and perceived fewer side effects of the method [43%]. The majority of acceptors [85%] were satisfied and desired continuous use. The most commonly experienced side effects were psychological effects [47%], but bleeding disturbances [64%], headache [54.5%] and weight changes [45.5%] were the most frequently cited reasons for discontinuation. Rumors contributed indirectly [25%] for stopping the method. Subdermal levonorgestrel implant is an acceptable method of contraception. Proper counseling and user support are important aspects to increase user satisfaction

Effect of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one on reproductive organs of the male laboratory mouse.

The effect of subcutaneous administration (10, 15 and 20 mg/kg body weight/day, for 21 days; and 20 mg/kg body weight/day, for 28 days) of 17 alpha-cyanomethyl-17 beta-hydroxy- estra-4, 9-dien-3-one (STS 557) on the male reproductive organs of the Parkes strain mouse was investigated. The effect of the treatment on the testis was not uniform; both regressed and normal seminiferous tubules were observed in the same section of the organ. Furthermore, the histological changes observed in the seminiferous tubules in testes of STS 557--treated mice were not different in different dosage groups. In general, in moderately affected seminiferous tubules, the germinal epithelium was thin and consisted of Sertoli cells, spermatogonia, spermatocytes and spermatids; such tubules showed presence of many vacuoles in the epithelium. In severe cases, the tubules had collapsed and were lined by mainly Sertoli cells, spermatogonia and spermatocytes. The treatment also caused marked depression in motility and concentration of spermatozoa in cauda epididymidis, weight of accessory sex glands and in the levels of sialic acid and fructose in the epididymis and seminal vesicle, respectively. By 56 days of drug withdrawal, the alterations induced in the reproductive organs returned to control levels, suggesting that STS 557 treatment induces reversible alterations in the male reproductive organs of Parkes strain mouse.

Effect of Norplant on liver function.

Combined pills have known adverse effects on liver function. Progesterone based contraceptives are thought to be safer in this regard. The effect of Norplant, a levonorgestrel contraceptive implant, on liver function was evaluated in 149 Bangladeshi women of reproductive age in this study. Liver function tests and ultrasonography of hepato-biliary system were done before and after the implantation. The patients were followed upto two years. There were non-significant transient rise of serum bilirubin and slight enlargement of liver during the first year. There was no significant change in the levels of AST, ALT, alkaline phosphatase, total protein, albumin-globulin ratio and prothrombin time. The results suggest that Norplant has no adverse effect on liver function.

Bone density in women receiving Norplant implants for contraception.

The aim of this study was to determine whether long-term Norplant uses is associated with changes in bone density. The study group consisted of forty one healthy women aged 19-42 years who had used Norplant for 31.1 +/- 11.2 months with a minimum period of 12 months. Fifty current IUD users constituted the control group. The bone density was measured by dual energy X-ray absorptiometry (DEXA) at the non dominant distal and ultradistal forearm. Serum estradiol was measured by microparticle enzyme immunoassay technique. Age, parity, income, weight, height and body mass index (BMI) of both groups were no differences. Our analysis did not find any differences in bone mineral density of distal forearm and ultradistal forearm between Norplant and IUD users (95% CI -0.01, -0.03 and -0.02, 0.02 respectively). Serum estradiol was not different in the two groups (95% CI -24.9, 110). This study revealed that the Norplant implants do not have any adverse effect on bone mineral density.