BACKGROUNDDepot 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.

METHODSThe 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.

RESULTSThere were no significant differences between groups at baseline in age, gynecologic age, body mass index (BMI), lumbar spine BMD and femoral neck BMD, etc. At 24 months of DMPA treatment, the mean percentage change from baseline in lumbar spine and femoral neck BMD values had decreased by 1.88% and 2.32%, respectively. The mean lumbar spine and femoral neck BMD in DMPA group at 24 months were not significantly different compared to baseline (P = 0.212 and P = 0.106, respectively). In comparison, in nonhormonal control group, there was a trend toward increasing BMD. At 24 months of observation, the mean percentage change from baseline in lumbar spine and femoral neck BMD had increased by 2.08% and 1.46%, respectively. There were no significant difference compared to baseline (P = 0.160 and P = 0.288, respectively). Mean BMD at the spine and femoral neck did not differ significantly between DMPA users and nonusers over 12-month, but the BMD values at both anatomical sites were significantly lower in DMPA users compared with nonusers after 24-month treatment (P = 0.009 and P = 0.009, respectively).

CONCLUSIONThe evidence of our study suggested that the use of DMPA for short-term (≤12-month) has no significant effects on BMD at spine and femoral neck, but long-term exposure to DMPA may prevent the bone mass accrual in adolescents.

Adolescent ; Bone Density ; drug effects ; Contraceptive Agents, Female ; pharmacology ; Female ; Humans ; Medroxyprogesterone Acetate ; pharmacology

To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects of 17-beta-estradiol (E(2)) 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, E(2), E(2)+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 E(2) could significantly enhance the expression of COX-2 continually. On the contrary, E(2)+MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E(2) 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.
Cyclooxygenase 2/genetics ; Cyclooxygenase 2/*metabolism ; Estradiol/*pharmacology ; Hela Cells ; Medroxyprogesterone Acetate/*pharmacology ; Uterine Cervical Neoplasms/*enzymology

OBJECTIVETo observe depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-week intervals for the suppression of spermatogenesis in healthy Chinese men.

METHODSAfter screening, 30 healthy volunteers were enrolled and randomly assigned to 3 dosage-groups (n = 10/group): 1000 mg TU (Group A), 1000 mg TU plus 150 mg DMPA (Group B), 1000 mg TU plus 300 mg DMPA (Group C). All dosages were given as intramuscular injections at 8-week intervals. The study consisted of an 8-week control (baseline) period, a 24-week treatment period and a 24-week recovery period.

RESULTSConsistent azoospermia or severe oligozoospermia was achieved and maintained in all the volunteers during the treatment period, except 2 in the mere TU group who experienced a "rebound" in sperm concentrations. An 8-week regimen of TU plus DMPA at both tested combination dosages effectively suppressed spermatogenesis to azoospermia. All volunteers tolerated the injections; no serious adverse effects were reported.

CONCLUSIONThe lower combined dosage is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.

Adult ; Androgens ; pharmacology ; China ; Gonadotropin-Releasing Hormone ; biosynthesis ; Humans ; Hypothalamo-Hypophyseal System ; metabolism ; Male ; Medroxyprogesterone Acetate ; pharmacology ; Prospective Studies ; Sperm Count ; Spermatogenesis ; drug effects ; Testosterone ; analogs & derivatives ; pharmacology

To assess the effects of a single supraphysiological postnatal administration of a progestogen on uterine glands in dogs, 10 females were randomly assigned to a medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within the first 24 h of birth. The safety of the treatment was also evaluated. A transient mild clitoris enlargement appeared in MPA-treated females. Microscopic postpubertal uterine assessment revealed the presence of uterine glands in all cases without significant differences in the area occupied by the glands per µm2 of endometrium nor in the height of the uterine epithelium.
Animals ; Animals, Newborn ; Clitoris/drug effects ; Dogs ; Epithelium/*drug effects ; Female ; Medroxyprogesterone Acetate/*pharmacology ; Organ Size/drug effects ; Random Allocation ; Sexual Maturation/drug effects ; Uterus/*drug effects

OBJECTIVETo study the effect of 17beta-estradiol (17beta-E(2)) and medroxyprogesterone acetate (MPA) on the expression of VEGF mRNA in epithelial ovarian carcinoma cell line in vitro.

METHODSHuman epithelial ovarian carcinoma cell line SKOV3 cells were exposed to 17beta-E(2) (10(-12) approximately 10(-8) mol/L) or MPA (10(-9) approximately 10(-5) mol/L), the expression level of VEGF mRNA was determined by RT-PCR.

RESULTSThe PCR products of VEGF were mainly 606 bp and 474 bp. The expression of VEGF mRNA in the 17beta-E(2)-treated cells was significantly higher than in the untreated control (P < 0.05), the expression level of VEGF mRNA increased with the increase in 17beta-E(2) concentration. The expression of VEGF mRNA in SKOV3 cells treated with MPA (10(-9) approximately 10(-5) mol/L) was significantly lower than in the untreated control (P < 0.05), especially that of 606 bp.

CONCLUSIONEstrogen can up-regulate, while progesterone can down-regulate mRNA expression of VEGF. Further studies are needed to elucidate the mechanism.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Hormonal ; pharmacology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Estradiol ; pharmacology ; Female ; Humans ; Medroxyprogesterone Acetate ; pharmacology ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

HOXA10 gene plays an essential role in differentiation of the endometrium and in human reproduction. The aim of this study was to investigate the regulatory effect of sex steroids and HB-EGF on HOXA10 gene in Ishikawa cells. Ishikawa cells were incubated with 17-beta estradiol (10(-8) mol/L), medroxyprogesterone acetate (MPA) (10(-6) mol/L), RU486 (10(-5) mol/L) or HB-EGF (10 ng/mL) for 48 h respectively. The expression of HOXA10 gene was detected by immunofluorescence, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Our results showed that either estrogen alone, progestin alone or progestin combined with estrogen could significantly increase the expression of HOXA10 gene 48 h after the treatment (P<0.05). But estrogen combined with progestin and RU486 could inhibit the up-regulation by estrogen and progestin. HB-EGF could elevate the expression of HOXA10 gene 48 h after the treatment (P<0.05). It is concluded that both estrogen and progestin can up-regulate the expression of HOXA10 gene in Ishikawa cells, but RU486 can inhibit the effect and HB-EGF can elevate the expression level of HOXA10 gene.
Cell Line, Tumor ; Endometrial Neoplasms/*pathology ; Estradiol/*pharmacology ; Genes, Homeobox ; Homeodomain Proteins/genetics ; Homeodomain Proteins/*metabolism ; Intercellular Signaling Peptides and Proteins/*pharmacology ; Medroxyprogesterone Acetate/*pharmacology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism

OBJECTIVESTo investigate the effect of administration of MPA with/without TU on serum sexual hormones and spermatogenesis of male rats.

METHODSTwenty rats had been classified into four groups. Each group received injection of saline(group A) or MPA(37.5 or 75 mg/kg) (group B or group C, respectively) or MPA (75 mg/kg) + TU (25 mg/kg) (group D) every month during three months. Data from serum sexual hormones (FSH, LH, T), sperm counting and motility had been collected and analysed.

RESULTSSpermatogenesis of rats undergoing administration of MPA with or without TU had been suppressed. Serum FSH and LH of group B, C, D declined, and so did serum T of group D. Testis of rats of group D atrophied and sperm counting of group D decreased remarkably compared with group B and C. But there was no statistics difference of the sexual hormone level among group B, C and D.

CONCLUSIONSAdministration of MPA alone could suppress the levels of FSH and LH and block the spermatogenesis of male rats. MPA combined with TU could offer stronger suppression on spermatogenesis. Mechanism of the suppression on spermatogenesis of MPA + TU is not only limited in the feed-back of gonadotropin, but there maybe exist a direct suppression on testis.

Animals ; Body Weight ; drug effects ; Drug Interactions ; Follicle Stimulating Hormone ; metabolism ; Gonadal Steroid Hormones ; blood ; Luteinizing Hormone ; metabolism ; Male ; Medroxyprogesterone Acetate ; pharmacology ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; drug effects ; Testosterone ; analogs & derivatives ; pharmacology

UNLABELLEDThis experiment was aimed to study the effects of different concentrations of medroxyprogesterone acetate (MPA) on proliferation, migration and apoptosis of endothelial progenitor cells (EPCs) in vitro and to provide experimental evidence for the use of MPA as anti-angiogenesis drug. We separated EPCs from bone marrow of a beagle dog and identified the expression of progesterone receptor (PR) in EPCs by immunocytochemistry. Proliferation tests (MTT analysis) were performed with EPCs in response to different concentration of MPA every 24 h for 7 consecutive days, the growth curve of these EPCs was obtained then. The inhibition rates were also obtained from MTT assay performed with EPCs exposed to different concentration of MPA. The migration tests were performed with EPCs in response to different concentrations of MPA. The cell cycle and apoptosis of EPCs exposed to different concentrations of MPA were analyzed by use of flow cytometry.

RESULTSImmunohistochemical staining showed that EPCs were positive to PR. High concentration of MPA had significant inhibition effect on the growth of EPCs. This effect was time- and dose-dependent. But the low concentration of MPA had not have such effect, EPCs exposed to high concentration of MPA were found arrested in S phase, and the apoptosis rate increased. The migration ability of EPCs exposed to high concentration of MPA was also damaged.

CONCLUSIONHigh concentration of MPA can induce EPCs' apoptosis and inhibit their growth and migration. All these biological effects of MPA may be achieved through PR on EPCs.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dogs ; Dose-Response Relationship, Drug ; Endothelial Cells ; cytology ; Female ; Medroxyprogesterone Acetate ; pharmacology ; Neovascularization, Physiologic ; drug effects ; Stem Cells ; cytology