Insulin resistance parameters in users of the injectable contraceptive depot medroxyprogesterone acetate during one year of use

Objectives The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA).

Methods A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (± 1 year) and body mass index (BMI; ± 1 kg/m²). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m², fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7.

Results The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months.

Conclusions HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non-obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference.     

Subclinical cardiovascular disease parameters after one year in new users of depot medroxyprogesterone acetate compared to copper-IUD

Purpose: To evaluate markers of cardiovascular disease in women with normal insulin sensitivity who had recently initiated use of depot medroxyprogesterone acetate (DMPA) as a contraceptive.

Materials and methods: A prospective, non-randomised, comparative study. Data of 30 women of 18–40 years of age, with normal hyperinsulinaemic–euglycaemic clamp at baseline and body mass index (BMI)?Results: The mean age of the women in the DMPA and IUD group was 28.7?±?6.5 and 28.3?±?5.8 years, respectively; the BMI was 23.0?±?3.4 and 24.3?±?2.7?kg/m², respectively, in the same groups. At 12 months, triglyceride levels were higher in the DMPA group compared to the IUD group and there was an increase in apolipoprotein B-100 in relation to baseline in DMPA group; there were no other difference between the groups.

Conclusions: No clinical cardiovascular effect was found but deterioration in CV markers was observed in the first year of use of DMPA.     

Body composition and weight gain in new users of the three-monthly injectable contraceptive,depot-medroxyprogesterone acetate,after 12 months of follow-up

Abstract

Objectives To evaluate weight gain and body composition (BC) in new users of depot-medroxyprogesterone acetate (DMPA) as a contraceptive.

Methods This cohort study followed up 20 DMPA users and 20 copper intrauterine device (TCu380A IUD) users, paired for age (± 1 year) and body mass index (BMI ± 1 kg/m²), during 12-months. Healthy, non-obese women aged 18 to 40 years, unaffected by conditions that could influence their body weight, were enrolled. Socio-demographic variables, habits, weight, BMI, BC using dual-energy X-ray absorptiometry, circumferences, skinfold thickness, body fat percentage and waist-to-hip ratio were evaluated. All participants were encouraged to adopt healthy habits.

Results At baseline, median age was 29 and 30.5 years, and mean BMI was 24.8 and 24.5 kg/m² in the DMPA and IUD groups, respectively. At 12 months, an increase was observed in waist and hip circumference in the DMPA users and 8/20 of them had a weight gain ≥ 5% (mean 4.6 kg) with accumulation of fat centrally.

Conclusions There were no differences in weight gain or in BC measurements between the groups; nevertheless 40% of women in the DMPA group had larger weight gain and accumulation of fat centrally. The duration of follow-up may have been insufficient to detect differences between the groups.

Chinese Abstract

摘要 目的 研究应用长效甲羟孕酮避孕对体重和身体成分的影响

方法 分别选取20名妇女开始使用长效甲羟孕酮避孕（DMPA组）以及20名开始使用含铜宫内节育器避孕（IUD组）进行队列研究,并按照年龄( ±1 岁)、体重指数（BMI± 1 kg/m² ）进行配对。40名18-40岁的健康、体重适宜、没有其他可能影响体重因素的妇女入选。记录研究对象的社会人口学特征、生活习惯、体重、体重指数、应用X线骨密度仪测量身体成分、手臂、腰、臀以及大腿的周径、皮肤褶皱的厚度、体脂的百分比以及腰臀比的数据。鼓励所有的研究对象选取健康的生活方式及饮食习惯。

结果 入选时两组妇女的平均年龄分别为29岁及30.5岁,体重指数分别为24.8kg/m²以及24.5 kg/m²。12个月后DMPA组的妇女有腰围和臀围的增加,8/20的妇女体重增加≥5%（平均4.6kg）伴有中央性脂肪蓄积的特点。

结论 使用DMPA以及使用含铜IUD12个月后的两组妇女在体重增加以及身体成分上的变化没有差异,但是DMPA组有40%的妇女有更多的体重增加以及体脂的中央性蓄积。研究可能需要更长的随访时间来发现两组的差异。     

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception

OBJECTIVE: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception. STUDY DESIGN: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment. RESULTS: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001). CONCLUSION: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.     

Effect of injectable medroxyprogesterone acetate and etonogestrel implants on GABA-A and serotonin receptors in white and gray matter of the brain: experimental study in rats

The aim of this study was to evaluate the time-dependent effect of progesterone-only contraceptives on the brain and to obtain an improved understanding of mood disorders experienced under this medication. A total of 66 Wistar albino rats were divided into three groups: etonogestrel (ENG) implant (group 1, n?=?30); depot medroxyprogesterone acetate (MPA)-injectable (group 2, n?=?30); and control (group 3, n?=?6) groups. Groups 1 and 2 were each divided into five subgroups, which were examined every 10?d for up to 50?d after medication administration, to evaluate its time-dependent effect. There was no difference in terms of gamma-aminobutyric acid (GABA) and serotonin immunohistochemical staining in white and gray matter among the subgroups of group 1. In group 2, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on day 50, when compared to the control group (p?=?0.041). When the subgroups of group 2 were compared, there was a significant decrease in serotonin receptor staining intensity in white and gray matter on days 40 and 50 when compared to day 10. In conclusion, we showed that ENG and MPA have no effect on apoptosis and GABA-A receptors in the brain. We also showed that MPA has time-dependent effects on serotonin receptors, which may be a possible mechanism involved in mood disorders during long-term usage of injectable progesterone-only contraceptives.     

甲羟孕酮对人卵巢癌耐顺铂SKOV3/DDP细胞株放射敏感性的影响

目的 研究人卵巢癌耐顺铂SKOV3/DDP细胞株对放射治疗的影响,及应用醋酸甲羟孕酮( Medroxyprogesterone Acetate,MPA)于SKOV3/DDP细胞株,探讨其对放射敏感性的影响及其可能机制。方法 以人卵巢癌SKOV3细胞株及其耐顺铂SKOV3/DDP细胞株为研究对象接受不同剂量的放射线照射,采用MTT法、克隆形成实验分析细胞相对存活率及放射抗拒性;应用非细胞毒性剂量MPA联合不同剂量放射线照射于SKOV3/DDP细胞,同法测定联合MPA作用后SKOV3/DDP细胞放射敏感性的变化,采用 Sigma Plot 10.0版软件,利用多靶单击模型S =1-(1-eD0/D)n拟合细胞存活曲线,计算放射相关参数。并采用流式细胞技术 (FCM) 检测细胞周期及凋亡情况。结果 随着放射剂量增大,SKOV3细胞和SKOV3/DDP细胞的相对存活率下降,以SKOV3细胞明显;二者的平均致死剂量(D0)分别为3.186和7.794,D0越大,放射抗拒性越强,表明耐药SKOV3/DDP细胞的放射抗拒性强于SKOV3细胞;同法测定MPA联合放疗组细胞的克隆形成率明显低于单纯放疗组,二者D0分别为4.040、7.794,放射增敏比为1.929。MPA联合放疗作用于SKOV3/DDP细胞,使其细胞周期阻滞于G0/G1期,S期细胞比例下降,并可以增加耐药细胞的凋亡率。结论 人卵巢癌SKOV3/DDP细胞具有放化疗交叉耐受性;MPA可以逆转SKOV3/DDP细胞对放射的抗拒性,其可能机制为促进细胞的凋亡,阻滞细胞周期进程。     

Comparison of two strategies for the administration of injectable depot medroxyprogesterone acetate: among women who returned to a family planning clinic at three- or six-month intervals

Objectives: The aim of this study was to compare the clinical performance of depot medroxyprogesterone acetate (DMPA) in women who received injections every 3 months at the Family Planning Clinic, and those who received every other injection at a health care facility near their place of residence, only returning to the clinic every 6 months.

Materials and methods: The medical charts of DMPA users from 2 January 1980 through 31 December 2012 were evaluated for this study. Two cohorts of women were created and compared: those who regularly received DMPA injections every 3 months (3-month group) at the clinic and those who received alternating 3-month injections at a health care facility near their residence house, returning to the clinic every 6 months for an injection (6-month group). In addition, effectiveness rates, reasons for discontinuation, and continuation rates were evaluated.

Results: Overall, 2637 women received all injections at 3-month intervals at the clinic, and 1190 women received every other injection at a health care facility near their residence. The women in the 3-month group had higher pregnancy rates and higher discontinuation rates (with the exception of discontinuation due to the loss of libido).

Conclusion: The women who received alternating injections near their homes were more likely to continue using DMPA as a contraception method and presented lower pregnancy and discontinuation rates (for the majority of reasons), when compared to those women who returned to the clinic every 3 months.     

Delayed first injection of the once-a-month injectable contraceptive containing 25 mg of medroxyprogesterone acetate and 5 mg of E(2)-cypionate: effects on ovarian function

OBJECTIVE: To assess whether women who were administered the first injection of DMPA+E(2)C on day 7 of their menstrual cycle (delayed injection) exhibit the same degree of ovarian suppression as women who receive it on day 5 of their menstrual cycle. DESIGN: Multicenter, randomized controlled trial. SETTING: Reproductive health clinics. PATIENT(S): Women aged between 18 and 38 years (inclusive) willing to use DMPA+E(2)C as their method of contraception. INTERVENTION(S): Participants received a DMPA+E(2)C injection on day 5 (control group, n = 41) or day 7 (delayed-injection group, n = 117) of their menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian activity and follicular development determined by serial serum progesterone levels and vaginal ultrasound. RESULT(S): Participants who received DMPA+E(2)C on day 5 of their menstrual cycle (control group) exhibited no more than limited follicular growth (no follicle >16 mm). Of those women who received DMPA+E(2)C on day 7 of their menstrual cycle (delayed-injection group), 21 (18%) showed some follicular growth, of whom 4 (3%) ovulated. CONCLUSION(S): The first injection of DMPA+E(2)C given on day 7 of a menstrual cycle does not provide the same inhibition of ovarian activity as that observed when it is administered on day 5 of the menstrual cycle.     

Teenagers requesting pregnancy termination are no less responsible about contraceptive use at the time of conception than older women

Teenage contraceptive use is often perceived as irresponsible, and Government initiatives are aimed at improving this. This prospective observational cohort study examined contraceptive use in 925 women requesting termination of pregnancy (TOP) and found that usage in all women, regardless of age, was poor with no difference between age groups. These findings challenge frequently made assumptions about irresponsible contraceptive use and imply that contraceptive education, and initiatives to tackle the growing number of TOPs, should not be confined to teenagers but should start in early adolescence and must continue well in to adulthood.