Inhibitory effect of medroxyprogesterone acetate on malignant growth of ovarian cancer 3AO cell line

Ovarian cancer 3AO cell line was treated with medroxyprogesterone acetate in vitro. The results showed that medroxyprogesterone acetate inhibited the growth of 3AO cell line. Three days after treatment, significant decrease in colony formation on the soft agar medium and subcutaneous transplant tumor formation in the nude mice were observed, and at the same time, C-erbB_2 expression in part of the 3AO cells decreased as analyzed by flow cytometry and immunohistochemical staining. Electron microscopic examination revealed certain degree of degeneration in part of the cells.

Concentration Changes of Medroxyprogesterone Acetate in Serum and Milk in Lactating Woman Who Used Depo Geston~

Objective To determine the concentration changes of medroxyprogesterone acetate （MPA） in serum and milk in the Chinese lactating women who used Depo Geston Methods Ten postpartum and breastfeeding women received an injectable contraceptive of Depo Geston （depo medroxyprogesterone acetate, DMPA, 150 mg/ampoule）. Serum and milk samples were collected in the 1^st, 2^st, 4^th, 6^th, 8^th 10^th and 12^th week after contraceptive injection. The concentrations of medroxyprogesterone acetate （MPA） in serum and milk were determined by radioimmunoassay. Results The highest MPA concentration in serum was observed at the 1^st week and then the level of serum MPA decreased obviously at the 2^na and 4^th week. After the 4^th week, the decline of serum MPA level slowed down. The concentration of milk MPA reached the highest level at 1^th week. But at the 2^nd week the average level of MPA in milk dropped by half The MPA concentration in the milk was changed in the range of 5.2-8.3 ng/mL in the following 10 weeks. During observation, the average ratios of concentration and area under curve （AUC） in milk/serum were both 0.55. There was a wide variation in MPA concentrations and ratios of milk/serum between subjects. Conclusion MPA concentrations maintained a certaim level at the 12^th week after DMPA injection. However, whether mather＇s intake of DMPA during feeding period has effect on children＇s growth, espcially pubertal growth, deserves further studies.

Development of Immunochemical Methods for Purification and Detection of the Steroid Drug Medroxyprogesterone Acetate

An immunochemical sol-gel-based immunoaffinity purification (IAP) method for purification and detection of the progestin drug medroxyprogesterone acetate (MPA) was developed. A polyclonal antibody (Ab) for MPA was generated, and two competitive (indirect and direct) sensitive enzyme-linked immunosorbent assays (ELISAs) for its detection were developed and implemented to determine the recovery and efficiency of the sol-gel based IAP method. The detection limits of the assays were 1.4 ± 0.2 ng·mL-1 (n = 4) and 4.0 ± 0.4 ng·mL-1 (n = 25) for the indirect and direct ELISAs, respectively. The Abs did not exhibit cross-reactivity with any other progestin or steroid hormone, with the exception of megestrol acetate, with which the Ab exhibited 76% cross-reactivity. The sol-gel IAP method successfully eliminated serum interference to a degree that enabled ELISA analysis of spiked serum samples. This method was also found fully compatible with subsequent chemical analytical methods, such as liquid chromatography followed by mass spectrometry (LC-MS/MS). The approaches developed in this study form a basis for analysis of MPA in biological samples and may be further used to study population exposure to MPA and to monitor MPA contamination in water samples.

Conservative Medroxyprogesterone Acetate Therapy in Early Stage of Endometrial Carcinoma Associated with Phosphatase and Tensin Homolog Expression

Young patients with the endometrial cancer IA who desire to preserve fertility, can select the conservative therapy with progestin. However, the therapy involves risks of progression and relapse. We examined immunohistochemical analyses of phosphatase and tension homolog (PTEN) and p53 expressions to predict the early relapse, and pregnancy and delivery. Twenty women with endometrial cancer, FIGO IA (1988) (FIGO staging was essentially defined post-surgically), instead of the pathogical specimen before surgery without myometrial invasion were estimated by MRI under 40 years at Gifu University Hospital, Japan from 1988 to 2009. Patients were treated with medroxyprogesterone acetate (MPA, 400 - 600 mg/day) for 4 - 10 months, with whole wall endometrial curettage performed every four weeks. Response to the therapy, pregnancy, delivery and relapse of disease during follow-up over a 72-month period. Immunohistochemical expression of PTEN and p53 was also evaluated with pregnancy, delivery and relapse rate. All patients had pathological complete remissions within 4 - 10 months. Relapse rate was high (60%) in more than 72 months. Immunohistochemical PTEN retain in tumor cells before MPA treatment (8/10) was significant better correlation with pregnancy and delivery rate than of lost cases (1/5) in non-obese women (P < 0.05). Conservative therapy is feasible in carefully selected young women with endometrial cancer without myometrial invasion. However, the relapse rate was high. In cases who desire to be a pregnant, an earlier infertility treatment may be considered especially for PTEN loss especially in nonobese cases.

Effect of Depot Medroxyprogesterone Acetate (DMPA) on Bone Mineral Density in Women of Reproductive Age

Objective To compare bone mineral density （BMD） between users of intramuscular depot medroxyprogesterone acetate（DMPA ） and nonhormonal control subjects. Methods The study included 68 women aged between 25 and 40 years using depot medroxyprogesterone acetate for 24 months and 59 women aged between 25 and 40 years using nonhormonal contraception as control subjects. BMD of the lumbar spine and femoral neck were obtained using dual energy X-ray absorptiometry. Results At 24 months of treatment, as compared with baseline, the mean BMD in lumbar spine and femoral neck was decreased by 5.5% and 5.9%, respectively. Lumbar spine and femoral neck BMD in women who used DMPA were significantly decreased compared with the subjects in nonuser （P〈0.001）. Conclusion These results show BMD declined during using DMPA in women aged 25 -40 years old.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.

Effect of depot medroxyprogesterone acetate on bone mineral density in adolescent women

Background Depot medroxyprogesterone acetate （DMPA） as a hormonal contraceptive is highly effective and widely used, but it may reduce bone mineral density （BMD） and increase the risk of osteoporosis. We compared BMD between users of intramuscular DMPA and nonhormonal subjects. Methods The study included 102 women aged between 16 and 18 years using DMPA for 24 months and 97 women aged between 16 and 18 years using nonhormonal contraception as nonusers control group. BMD of the lumbar spine and femoral neck was measured every 12 months for 24 months using dual-energy X-ray absorptiometry, comparing mean BMD changes in DMPA users and nonusers.

Changes in bone mineral density among women aged 19-24 years using injectable contraceptive depot medroxyprogesterone acetate

Objective To compare bone mineral density （BMD） between users of intramuscular depot medroxyprogesterone acetate （DMPA） and nonhormonal control subjects. Methods The study included 87 women aged between 19 and 24 years using DMPA （DMPA group）for 24 months and 83 same-age women using nonhormonal contraception as control group. BMD of the lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry, comparing mean BMD changes in DMPA group with the control. Results After 24 months of DMPA treatment, as compared ~ith baseline, the mean BMD in lumbar spine and femoral neck were decreased by 2.67% and 2.71%, respectively. The mean lumbar spine and femoral neck BMD in DMPA group at 24 months were not significantly different compared with baseline （P=0. 080 and P=0. 076, respectively）. In comparison, in control group, there was a trend toward increasing BMD. After 24 months of observation, the mean percentage changes from baseline in lumbar spine and femoral neck BMD were increased by 1.24% and 1.30%, respectively. There was no significantly difference compared with baseline （P=0. 436 and P=0.373, respectively）. Mean BMD at the spine and femoral neck did not differ significantly between DMPA users and nonusers over 12 months （P=0.153 and P=0.140, respectively）, but the BMD at both anatomical sites was significantly lower in DMPA group than in the control after 24 months of treatment （P=0.012 and P=0.008, respectively）. Conclusion The use of DMPA for short-term （≤12-month） had no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA had significant loss in BMD in women aged between 19 and 24 years.

Effect of depot medroxyprogesterone acetate(DMPA) on bone mineral density(BMD) and evaluating changes in BMD after discontinuation of DMPA in adolescent women

Objective To compare bone mineral density （BMD） between users of intramuscular depot medroxyprogesterone acetate （DMPA） and nonhormonal subjects and evaluated the changes in BMD after discontinuation of DMPA.Methods The study included 102 women aged 16-18 years using DMPA for 24 months and 97 same-age nonusers. BMD of the lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry. The mean BMD values were compared between DMPA users （DMPA group） and nonusers （control group） and the changes of BMD during 36 months after discontinuation of DMPA were observed.Results Mean BMD at the spine and femoral neck did not differ significantly between DMPA group and control group over 12 months, but the BMD values at both anatomical sites were significantly lower in DMPA group than in control group after 24 months treatment. After DMPA discontinuation, the mean BMD values in DMPA users increased substantially. At 24 months after DMPA discontinuation, there were no significant differences between DMPA group and control group. But the values of the lumbar spine and femoral neck BMD in DMPA group were still 1.70% and 1.87%, respectively, below nonusers at 36 months after DMPA discontinuation.Conclusion The use of DMPA for short-term （ ≤12 months） had no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA had significant loss in BMD in adolescents. Bone loss occurring with DMPA use is reversible after DMPA discontinuation.

大气压化学电离质谱法测定饲料中的醋酸甲羟孕酮

醋酸甲羟孕酮(medroxyprogesterone acetate)是一种人工合成生长激素,一般被用来生产避孕药及补充人体激素,但是如果使用过量,将影响生育功能.欧盟已经明令禁止在食物和饲料中使用醋酸甲羟孕酮.……

The Expression of Cyclooxygenase-2 in Cervical Cancers and Hela Cells Was Regulated by Estrogen/Progestogen

To investigate the relationship between the expression of cyclooxygenase-2 （COX-2） and menstrual cycle, the regulatory effects of 17-β-estradiol （E2） and medroxyprogesterone acetate （MPA） on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system. Hela cells were incubated with alcohol, E2, E2＋MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction （RT-PCR）. Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase （P〈0.05）, but there was no difference in the positive rate between proliferative phase and secretory phase （P〉0.05）. Incubation with E2 could significantly enhance the expression of COX-2 continually. On the contrary, E2＋MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E2 group （P〈0.05 and P〈0.01 respectively）. It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.

Studies on the Effects of Steroid Hormone Contraceptives on Lipid, Lipoprotein and Apolipoprotein Metabolism in Chinese Women

Objective To explore the effects of steroid hormone contraceptives (SHCs), such as Mercilon, Chinese No. 1 pill, Post coital pill, Mesigyna, and Cyclofem, on lipid metabolism in Chinese women during the last decade Materials & Methods A total of 122 healthy volunteers who requested contraception were recruited in the study and one of the above mentioned SHCs was administered.Fasting serum samples were taken from each subject before, during and after treatments. Triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL c), low density lipoprotein cholesterol (LDL c), Apolipoprotein A I, A II and B were measured. The changes in the ratios of TC/HDL c, Apo A I/Apo B were also observed. Results Although the levels of lipid were either increased or decreased by any one of the 5 contraceptives, these changes recovered after withdrawal of the drug administration. No significant changes were detected in the ratios of TC/HDL c, Apo A I/Apo B during treatments. Conclusion The results suggest that there is no obvious impact on lipid profile induced by any of the 5 contraceptives within one year. The induced effects on lipid metabolism could be reduced by alternate use of 2 contraceptives with different biological activities.

Combined effects of MPA and EBRT in stage Ic endometrial cancer patients

Objective： To report the comparative effect of combined medroxyprogesterone acetate （MPA） and external beam pelvic radiotherapy （EBRT） with EBRT alone on local or distant recurrences, overall survival and treatment related toxicities in patients with stage Ic grade 3 endometrial cancer. Methods： A retrospective review of 80 International Federation of Gyne- cology and Obstetrics （FIGO） stage Ic grade 3 endometrial carcinoma patients treated between October 1994 and October 2004 at Renmin Hospital, Wuhan University, China was performed. All patients underwent surgery, of which 40 patients in arm I received combined MPA and EBRT while in arm II 40 patients received only adjuvant EBRT after surgery. The median dose of EBRT in arm I was 50 Gy （range 36-54 Gy） and in arm Ⅱ was 45.2 Gy （range 43.2-50.4 Gy）. Multivariate analysis was performed for the prognostic factors and Kaplan-Meier method was used for overall survival. Results： Of the 80 eligible patients, 40 in each group could be evaluated. The follow-up times ranged from 4-98 months with a median of 45 months. The overall survival rates at five years were 73% among patients treated with combined MPA and EBRT and 28.2% among patients treated with EBRT alone （P 〈 0.001）. The rate of distant metastasis was significantly higher among patients treated with EBRT alone group than combined MPA and EBRT （55% vs 25%, P = 0.006） while no difference in Ioco regional recurrence rates was observed in both treatment groups. Most of the side effects observed in the combined MPA and EBRT group. Age （P 〈 0.001） and the presence of progesterone receptors （P = 0.003） were independent significant prognostic factors for overall surviva} in multiple regression analysis. Conclusion： We has been concluded that the addition of progestagen to external beam pelvic radiotherapy significantly improved survival and reduced distant metastasis among women with stage Ic grade 3 endometrial cancer.

The Use of Hormonal Contraceptives and Preeclampsia among Ghanaian Pregnant Women

Hormonal contraceptives (HC) are thought to play a role in the pathogenesis of cardiovascular diseases. The study evaluated the use of HC as a primary cause of preeclampsia (PE) among Ghanaians. This study comprised 30 preeclamptic women and 30 healthy normotensive pregnant women with over 20 weeks of gestation at the Comboni Hospital, Ghana using a randomized case-control study. Blood pressure, weight, height, socio-demographics, medical and previous obstetric history were taken and recorded. Blood samples were collected for the estimation of homocysteine and fasting lipids. Estimated foetal weight (EFW) and infant birthweight (BWT) were obtained from maternal records. This study was carried out in 2019. 80.0% of women with PE used the hormonal contraceptive “depot medroxyprogesterone acetate” (DMPA) prior to pregnancy. The use of DMPA was associated with about thirty-fold increase in the odds of developing PE (OR = 29.71, p < 0.001). Systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), triglycerides (P = 0.024), LDL-C (P = 0.026), and homocysteine levels (P < 0.001) were significantly elevated in the PE cases than the normal pregnant (NP) women, whilst EFW (P < 0.001), BWT (P < 0.001) and HDL-C levels (P = 0.001) were significantly reduced in the PE cases when compared to NP women. 50% and 47% of PE cases had intrauterine growth restriction and low birthweight infants, respectively. In conclusion, DMPA use predisposes women to a high risk of developing PE. DMPA could partly contribute to endothelial dysfunction, hyperhomocysteinaemia, dyslipidaemia and excessive weight gain, all of which characterize PE.

Percutaneous estrogen in prevention of early postmenopausal bone loss in Chinese women

OBJECTIVE: To identify the optimal dosage of 17beta-estradiol gel + oral progestin for preventing bone loss in postmenopausal Chinese women. METHODS: A 3-year open label, randomized, prospective clinical trial was conducted. Sixty healthy women who had been postmenopausal for 1 to 5 years were recruited and divided into following 4 groups: group 1, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus micronized progesterone (MP) 100 mg/d; group 2, percutaneous gel 17beta-estradiol (E(2)) 1.5 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d; group 3, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus micronized progesterone (MP) 100 mg/d; and group 4, percutaneous gel 17beta-estradiol (E(2)) 0.75 mg/d plus medroxyprogesterone acetate (MPA) 2 mg/d. Estrogen and progestin were given continuously for 25 days per month. Bone mineral density (BMD) was measured using quantitative computed tomography (QCT) for trabecular bone of L2-5 and dual energy X-ray absorptiometry (DEXA) for L2-4 and hip 5 times during the trial at baseline and at the 6-, 12-, 18-, 24- and 36-month visits. RESULTS: Fifty-nine patients (98.3%, 59/60) stayed in the study for 1 year, 56 patients (93.3%, 56/60) for 2 years, and 51 (85%, 51/50) for 3 years. On average, menopausal symptoms were relieved by 80% after 6 months of treatment. By the 24th month, the mean increase in BMD ranged from 4.3% to 7.5% in trabecular bone; and by the 36th month, it ranged from 4.2% to 6.2% in L2-4 and 1.61% to 3.77% in the neck. There were significant difference after treatment (P 0.05) was found in improvement of symptoms, levels of bone markers or BMD. CONCLUSION: A daily dose of estradiol gel, either 0.75 mg or 1.5 mg, is effective in preventing early postmenopausal bone loss and relieving menopausal symptoms. After 3-year treatment, spinal BMD could increase steadily, so does hip BMD, especially in the first 2 years.

A comparison of two different dosages of conjugated equine estrogen in continuous combined hormone replacement therapy with progestin

To investigate the effects of two different dosages of conjugated equine estrogen (CEE) on preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause Methods A total of 236 postmenopausal women were randomly allocated to one of the following groups: Group A: 0 625 mg CEE+2 mg medroxyprogesterone acetate (MPA)+1 tab Caltrate-D per day; Group B: 0 3 mg CEE+2 mg MPA+1 tab Caltrate-D per day; Group C: 1 tab Caltrate-D per day as the control group The study was continued for 2 years The following parameters were monitored: ① L2-4 bone mineral density (BMD) (measured with dual energy X-ray absorptiometry (DEX)), ② menopausal syndr ome improvement (assessed by comparing Kupperman scores), ③ vaginal bleeding rate, and the thickness of the endometrium and breast in each group Results Overall, 213 cases (90%) completed the 1-year study and 176 cases (75%) completed the 2-year study The percentage changes in L2-4 BMD at the 12th and 24th month in Group A were +2 3% and +3 7%, respectively, with the posttreatment values being significantly higher than pretreatment values (P<0 001) The percentage changes were +2 7% at 12th month (P<0 05) and +0 7% at 24th month (P>0 05) in Group B And that of Group C were -0 4% at 12t h month and -1 6% at 24th month (P>0 05) L2-4 BMD in both Group A and B w as significantly higher than that in Group C at 12th and 24th month (A vs C, P<0 001; B vs C, P<0 05) Kupperman Sco res were significantly reduced after 1, 3, 6 ,12 and 24 months in all 3 groups when compared with baseline (P<0 001) Scores in Group A and Group B were significantly lower than that in Group C (P<0 001) However, the vaginal bleeding rates in Group A were significantly higher than that in Group B or in Group C There was no atypical hyperplasia of endometrium in the 3 groups by the end of the study One p atient in Group A developed superficial thrombophlebitis by the end of 12th month Conclusion Continuous combination of CEE and MPA is effective in preventing bone loss and relieving the symptoms of menopausal syndrome in women at an early stage of menopause The vaginal bleeding rates in the Group treated with 0 625 mg/d CEE were significantly higher than those treated with 0 3 mg/d CEE

Dual-specificity Phosphatase 1 Deficiency Induces Endometrioid Adenocarcinoma Progression via Activation of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Pathway

Background： Previously, we reported that dual-specificity adenocarcinoma （EEA）. However, the role of DUSP1 medroxyprogesterone （MPA） are still unclear. phosphatase I （DUSPI） was differentially expressed in endometrioid in EEA progression and the relationship between DUSPI and Methods： The expression of DUSPI in EEA specimens was detected by immunohistochemical analysis. The effect of DUSPI on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. MPA-induced DUSPI expression in EEA cells was measured by Western blot. Results： DUSPI expression was deficient in advanced International Federation of Gynecology and Obstetrics stage, high-grade and myometrial invasive EEA. In EEA cell lines （HeclA, Hecl B, RL952, and Ishikawa）, the DUSP1 expression was substantially higher in lshikawa cells than in other cell lines （P 〈 0.05）. Knockdown ofDUSP I promoted lshikawa cells proliferation, migration, and activation of mitogen-activated protein kinases/extracellular signal-regulated kinase （MAPK/Erk） pathway. MPA-induced DUSP1 expression and inhibited MAPK/Erk pathway in Ishikawa cells. Conclusions： Our data suggest that DUSP1 deficiency promotes EEA progression via MAPK/Erk pathway, which may be reversed by MPA, suggesting that DUSP I may serve as a potential therapeutic target for the treatment of EEA.