SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The purpose of this study was to examine estradiol and bone mineral density (BMD) in a cohort of adolescents using depot medroxyprogesterone acetate (DMPA) for one to two years. BMD was significantly decreased in the femoral neck and lumbar spine at year one. Estradiol levels suggested hypoestrogenization among subjects
PURPOSE: To compare attitudes and practices related to clinicians' use of depot medroxyprogesterone acetate [Depo-Provera (DMPA)] and levonorgestrel implants in adolescents in three northern European countries and the United States. METHODS: Between the fall of 1993 and the winter of 1995, surveys eliciting clinician attitudes and practices with the two contraceptive methods were collected from practitioners who provide contraceptive care to teens in Sweden (n = 282), The Netherlands (n = 197), Great Britain (n = 108), and the United States (n = 548). RESULTS: Clinicians in Great Britain and the United States reported prescribing of DMPA, selected DMPA in their top three choices for contraception in teens, and had patients ask about DMPA more frequently than clinicians in Sweden or The Netherlands (p < 0.0001). U.S. clinicians were more likely to report prescribing of the implants, list them as a top choice, and have patients ask for it more frequently than were providers in the other three countries (p < 0.0001). Noncompliance with previous contraceptives was the most common indication for use of either method in this age group. "Worst fears" with DMPA use included infertility, particularly among Swedish clinicians (p < 0.0001), as was pregnancy and loss to follow-up, particularly among British clinicians (p < 0.0001). Condom nonuse was a concern associated with both methods. Breakthrough uterine bleeding was a concern related to implant use, particularly among Swedish practitioners (p < 0.0001). CONCLUSION: Clinicians in the United States and Great Britain display more enthusiasm toward the use of the long-term progestins in adolescents than do clinicians in Sweden or The Netherlands. Continuing education programs could be designed to educate clinicians to allay their concerns about these contraceptives in countries where teen pregnancy is considered a problem.
STUDY OBJECTIVE: Depot-medroxyprogesterone acetate (DMPA) is thought to cause changes in mood among patients using it for contraception. The purpose of this study was to evaluate changes in negative and positive affect among adolescent females using DMPA as a contraceptive agent. DESIGN, SETTING, PARTICIPANTS: This prospective study was set in an urban hospital adolescent clinic. Thirty-nine adolescents choosing DMPA as a contraceptive agent and 24 adolescents not using any hormonal contraception were enrolled as subjects and controls, respectively. Two standardized questionnaires, the Beck Depression Inventory (BDI) and the Multiple Affect Adjective Checklist-Revised (MAACL-R), were administered at baseline to all participants and readministered at 3, 6, and 12 months. MAIN OUTCOME MEASURES: Changes in negative affect from baseline to 3, 6, and 12 months were evaluated by the BDI and by "dysphoria" subscale scores of the MAACL-R. Paired t-tests were used to measure these changes in subjects and controls separately. RESULTS: The mean change in BDI scores from baseline to one year for those who completed one year was -4.8 for subjects (P =.02) and +.3 (P =.84) for controls. The mean change in the dysphoria subscale scores was -5.7 (P =.21) for the subjects and -.1 (P =.98) for the controls while the change in the positive affect scores over a period of one year were -2.1 (P =.46) and +.1 (P =.98) for subjects and controls, respectively. CONCLUSIONS: Adolescents using DMPA do not show depressive symptoms when using DMPA as a contraceptive agent over a period of 12 months as measured by the BDI and show no significant changes in negative or positive affect as measured by the MAACL-R.
STUDY OBJECTIVE: To determine if factors such as body mass index (BMI), race, and age are associated with weight gain in adolescents receiving depot medroxyprogesterone acetate (DMPA). DESIGN/SETTING: Retrospective chart review at three rural health department family planning clinics and a university-based adolescent clinic in rural eastern North Carolina. PARTICIPANTS: Adolescent females, aged 12-19, who used either oral contraceptive pills (OCPs) or DMPA consistently for the first year of use. MAIN OUTCOME MEASURE: Weight change at one year. RESULTS: A total of 239 adolescent females were included in the analysis; 117 were DMPA users and 122 were OCP users. The mean weight gain for the DMPA group was 8.9 lbs. compared with 4.79 lbs. in the OCP group (P =.002). The change in BMI from baseline was greater among the DMPA group (1.51 +/- 1.94) than the OCP group (.75 +/- 1.65), P =.001. After adjusting for age, race, and contraceptive method, initial BMI was associated with weight gain (P =.009). CONCLUSIONS: Adolescent females using DMPA gained significantly more weight over one year than those girls using OCPs. Adolescent females who are overweight at the initiation of DMPA may be more likely to have significant weight gain during the first year of use.
STUDY OBJECTIVE: To document physical and symptomatic changes in adolescent females using depot medroxyprogesterone acetate (DMPA) for contraception. DESIGN: A 30-month prospective experimental study using a convenience sample of subjects. SETTING: A pediatric primary care clinic in Milwaukee, Wisconsin that serves an urban population of low socioeconomic status. PARTICIPANTS: A mostly African-American group of 53 patients (mean age 16.5 +/- 1.3 years). INTERVENTIONS: Subjects received 150 mg DMPA intramuscularly in either the deltoid or gluteus muscle. The first two DMPA injections were given 6-8 weeks apart in an effort to decrease menstrual irregularity. Subsequent injections were given every 3 months. A questionnaire was administered at each visit to document physical and symptomatic changes. MAIN OUTCOME MEASURES: Included weight change, frequency and amount of menstrual bleeding, and perceived side effects and satisfaction both documented with a 5-point Likert scale. RESULTS: At 5, 11, and 17 months of DMPA use, 75%, 40%, and 19% of subjects continued DMPA. The most commonly perceived side effects were weight gain (27%), headache (25%), irregular periods (24%), fatigue (23%), abdominal pain (18%), and decreased sexual desire (15%). Significant weight gain was noted with an average increase of 6.0 +/- 6.0 kg at 11 months of DMPA use and 9.0 +/- 5.4 kg at 17 months. No menstrual bleeding was experienced by 30%-40% of adolescents in any 3-month injection period, and those who bled averaged 8-13 days of bleeding between injections. No pregnancies occurred and 87% of patients were either satisfied or very satisfied with DMPA as a method of contraception. CONCLUSION: Despite the documented side effects, DMPA is an effective, acceptable contraceptive for some adolescent females who are at high risk for pregnancy.
We previously showed that medroxyprogesterone acetate (MPA) effectively decreases the arterial CO(2) levels in postmenopausal women with partial upper airway obstruction. The aim of the present study was to analyze the effects of MPA on the inspiratory flow shapes during sleep. Eight postmenopausal women with hypoxemia and partial upper airway obstruction during sleep (patients) received MPA 60 mg daily for 14 days. Four matched postmenopausal women without MPA treatment served as controls. Sleep and nasal pressure were recorded on each visit. Each breath was analyzed for duration, volume and inspiratory flow shape class. MPA shortened inspiration and prolonged expiration. The inspiratory volumes increased consistently in all flow shape classes. The inspiratory shapes with single late peak were transformed to those with double peak. MPA also decreased shapes with mid-peak or mid-plateau. MPA did not have an effect on sleep. Sleep modified the flow shape distribution only in patients but in a similar fashion in stages S2, SWS and REM. The results suggest that postmenopausal women present with a significant proportion breaths with poor initial inspiratory flow, which is reversed with MPA-induced respiratory stimulation.
The purpose of this work was to examine the mammary glands of adult, ovariectomized female cynomolgus macaques (Macaca fascicularis) in a long-term study of the effects of hormone treatments on chronic disease. Treatments included conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE+MPA, and tamoxifen. Doses were scaled from those given women. Treatments were given in the diet for three years, followed by necropsy and tissue collection. Endpoints evaluated included glandular histology, histomorphometry, and immunohistochemical detection of the proliferation marker Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in mammary epithelial cells. Major findings were as follows: CEE induced PR expression and focal to diffuse lobuloalveolar proliferation. Proliferation was increased by the addition of MPA, but was not induced by MPA alone. Tamoxifen induced ER and PR but not Ki-67 expression or glandular hyperplasia. Neoplasms were not seen. These findings indicate that progestogens may exacerbate, not antagonize mammary gland proliferation induced by estrogen replacement therapy, and that tamoxifen has both estrogen agonist and antagonist effects on sex steroid receptor expression in the normal primate breast.
The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3-weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent-to-treat analysis (p = 0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p = 0.012). Seven patients were removed from MPA due to side effects. The changes in patient-rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p = 0.39). In conclusion, in patients with advanced breast cancer achieving remission or non-progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.
The level of parathyroid hormone-related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard beta-actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P < 0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P < 0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 x 10(-8) M of estradiol (E2), 1 x 10(-6) M of tamoxifen (TAM) and 1 x 10(-5) M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P < 0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
The effect of medroxyprogesterone acetate (MPA) on the mitotic activity of bone marrow and testis during chemotherapy was investigated experimentally in an animal study. A total of 120 male Swiss albino mice were included in this study. Six groups were formed, each consisting of 20 mice. Low-dose MPA (LD-MPA) (15 mg/kg), high-dose MPA (HD-MPA) (100 mg/kg), LD-MPA plus cyclophosphamide (CP) (65 mg/kg), HD-MPA plus CP (65 mg/kg), and CP (65 mg/kg) were administered to the test groups and no drug was administered to the control group. Bone marrow samples and testis were examined for mitotic activity rate (MAR) on days 0, 18, 22, 26, and 30. In groups with regimens containing CP, MAR of hematopoietic cells in bone marrow was suppressed significantly (p<0.05). There was no difference in MAR of hematopoietic cells in bone marrow between the groups given MPA or not (p>0.05). Mitotic activity rate of the testis cells was significantly suppressed in groups with regimens containing MPA (p<0.05). In conclusion, MPA inhibited mitotic activity of testis, but there was no effect on the mitotic activity of bone marrow. These data do not seem to confirm the hypothesis of a myeloprotective effect of MPA.
Several reports suggested that steroidogenic hormones could be directly involved in the regulation of apoptosis in vitro, but whether this is due to blocking or promoting mechanism of these hormones remains controversial. However, it was shown that progesterone exhibited a protective effect against the apoptotic process during mouse mammary gland involution in vivo. In this study, we analyzed the effect of medroxyprogesterone acetate (MPA) treatment, an agonist of progesterone, on serum starvation induced apoptosis on breast cancer cell lines. Positive and negative progesterone receptor (PgR+ and PgR-) breast cancer cell lines were treated with MPA (10 nM), either in standard culture conditions or in serum-free medium to induce apoptosis. Cell survival, proliferation and apoptosis were simultaneously analyzed with the expression of apoptosis-related genes measured by a real time quantitative RT-PCR. At non cytotoxic doses, MPA protected PgR+ T47-D, MCF-7 and H466-B cell lines against serum depletion-induced apoptosis, while MPA did not protect PgR-MDA-MB-231 cells against serum depletion induced apoptosis. In PgR+ cell lines and in concordance with the protective effect, the pro-apoptotic HRK and BAK1 mRNAs were up-regulated after apoptosis induction, while they were no more induced in condition of protection against apoptosis after MPA treatment. We also observed, specifically in PgR+ cells, an up-regulation of BCLX-L and BCLX-S and a down-regulation of BCL2 mRNAs, which are specific to the MPA response and unrelated to apoptotic process. Involvement of these genes with regard to the MPA-mediated protection against apoptosis is discussed.
Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PR(A) isoform as compared with PR(B), as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immunohistochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.
Eighty patients with advanced metastatic renal cancer have been treated with hormones, chiefly medroxyprogesterone acetate (Provera). This progestational compound is remarkably free from side-effects and can be given in high dosage for long periods without serious complications. Ninety per cent of cases had multiple metastases: in 76% more than one organ was involved and nearly 50% were seriously ill or "terminal".Subjective improvement occurred in at least 55%. In 11 patients there was marked improvement in the radiological or clinical signs of tumour within 2 to 6 weeks of commencing treatment or changing to a different hormone. In two further cases improved general health was associated with stationary metastases for 20 months. A significant objective response occurred in 16% of the total series. A favourable response was seen more often in men (21%) than in women (8%). If deaths within 6 weeks are excluded the objective response rate in men is increased to 27%. Although the response of advanced renal cancer to hormonal treatment is usually incomplete and of brief duration, it is possible for such treatment to offer a "new lease of life" to a seriously ill patient, even in old age, for 2 to 3 years.
Navelbine (NVB, vinorelbine ditartrate, KW-2307), a new vinca alkaloid analogue, has been shown to be clinically effective against advanced breast cancer. In this report, the combined effect of NVB with medroxyprogesterone acetate (MPA), a synthetic progesterone derivative, was examined in vitro against human breast carcinoma MCF-7 cells. The combined effect was demonstrated to be synergistic using the isobologram and median-effect plot analyses. To elucidate the mechanism of action, we further examined effects of both drugs on cell cycle distribution of the cells in combination and/or alone. NVB at 2 nM induced apparent G1-phase accumulation as well as the induction of cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1) protein and the dephosphorylated form of retinoblastoma protein (pRb). In contrast, MPA at 0.1 microM also induced G1-phase accumulation as well as the reduced expression of cyclin D1 protein. In addition, the combination of both drugs induced augmented G1-phase accumulation, which occurred along with p21(WAF1/CIP1) protein induction, cyclin D1 protein reduction and pRb dephosphorylation. These results demonstrate that the synergistic combined effect of NVB with MPA was mediated through enhancement of G1-phase accumulation that resulted from the different action point(s) of each drug. Furthermore, the synergistic combined effect of NVB with MPA was also observed in other human breast carcinoma cell lines, such as T-47D and ZR-75-1. These results suggest that combination therapy of NVB with MPA in breast cancer might be effective in clinical studies.
Interleukin 6 (IL-6) is a multifunctional cytokine. Recent reports suggest that circulating IL-6 secreted from tumour cells plays an important role in cancer-induced cachexia. Medroxyprogesterone acetate (MPA) has been used as an endocrine therapeutic agent for patients with breast cancer. It has been suggested that MPA decreases serum IL-6 levels and preserves the bodyweight of patients with advanced breast cancer. However, the mechanisms of action responsible for the anticachectic effect of MPA have not been elucidated. Therefore, the effects of MPA on IL-6 secretion were studied both in vitro and in vivo using a human breast cancer cell line, KPL-4, which secretes IL-6 into medium and induces cachexia when injected into female nude mice. MPA (10-1000 nM) dose-dependently decreased basal IL-6 secretion into medium, and also suppressed tumour necrosis factor (TNF-alpha)-induced IL-6 secretion. Both basal and TNF-alpha-induced IL-6 mRNA levels were dose-dependently lowered by MPA. Moreover, intramuscular injections of MPA (100 mg kg(-1) twice a week) into nude mice bearing KPL-4 transplanted tumours significantly decreased serum IL-6 levels without affecting tumour growth and preserved the bodyweight of recipient mice. These findings suggest that suppression of IL-6 secretion from tumour cells, at least in part, causes the anticachectic effect of MPA.
OBJECTIVE: To compare longitudinal changes in weight, body fat, and ratio of central to peripheral fat mass among first-time depot-medroxyprogesterone acetate (DMPA) users to women using no hormonal contraception, and to evaluate user characteristics associated with that change. DESIGN: Prospective longitudinal study. SUBJECTS: Healthy women, aged 18-35 y, using DMPA for contraception (n=178) and women using no hormonal contraception (n=145). MEASUREMENTS: Weight, body fat, and the central distribution of fat, measured at 3-month intervals for 30 months, by electronic scale and dual-energy X-ray absorptiometry (DEXA). The ratio of central to peripheral distribution of body fat was computed by dividing the body fat in the conventional DEXA trunk region of interest (ROI) by the ROI's that encompass the arms, hips and legs. RESULTS: Women using DMPA had a significantly greater increase in all measures of fatness than women using no hormonal method of contraception (P<0.03). The observed weight of DMPA users increased from a mean of 69.4 kg (s.d.=16.9) at baseline to 75.5 kg (s.d.=25.0) at 30 months; an increase of 6.1 kg (8.8.%). Fat mass increased from a mean of 25.3 kg (s.d.=12.6 kg) at baseline to 31.4 kg (s.d.=17.8); an increase of 6.1 kg (23.6%) in DMPA users. The ratio of central to peripheral fat mass in DMPA users changed from 0.95 (s.d.=0.155) at baseline to 1.01(s.d.=0.198) at 30 months. In contrast, weight, fat mass and the ratio of central to peripheral fat mass of control participants remained virtually unchanged over the same time period. Women with higher baseline physical activity levels had a smaller increase in body fat (P=0.003) and the fat ratio (P=0.03), but not weight (P=0.48). No other user characteristics including, smoking, past oral contraceptive use or previous pregnancies predicted change in level of fatness. CONCLUSIONS: This study has demonstrated a change in body composition toward greater fatness and toward a central redistribution of fat among DMPA users as compared to controls and provides important information to be used when counseling women regarding contraceptive methods. Given the potential long-term implication of these changes, further study is recommended to determine whether the gains in fatness are reversed following DMPA discontinuation and to examine the role of progestins in the development and maintenance of obesity.
The reason that estrogen is strongly protective in various estrogen-deficient animal models while seemingly detrimental in postmenopausal women remains unclear. It hypothesized that prolonged oral medroxyprogesterone (MPA) plus oral conjugated equine estrogens (CEE) diminishes estrogen ability to reduce stroke damage in the rodent stroke model. To test the hypothesis, we fed ovariectomized rats CEE or MPA, or a combination of CEE and MPA (CEP), before inducing 120 min of reversible focal stroke, using the intraluminal filament model. After 22 h reperfusion, the brains were harvested and infarction volumes were quantified. Treatment with CEE alone or with CEP reduced cortical infarction volume. However, CEP failed to provide ischemic protection in subcortical regions. It was concluded that CEE alone, or with CEP, is neuroprotective in the cortex, but interactive effects between the hormones may counteract CEE beneficial effects in subcortical brain regions.
OBJECTIVE: This study was designed to compare with placebo the dose-response effect of cyclical doses of the C21 progestogen, medroxyprogesterone acetate (MPA) on blood pressure (BP) when administered to normotensive postmenopausal women receiving a fixed mid-range daily dose of conjugated equine oestrogen (CEE). MATERIALS AND METHODS: Twenty normotensive postmenopausal women (median age 53 years) participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each of 4 weeks duration. The four blinded treatments were MPA 2.5 mg, MPA 5 mg, MPA 10 mg and matching placebo, taken for the last 14 days of each 28 day treatment cycle. CEE 0.625 mg was also administered once daily as open labelled tablets to all subjects throughout the study. Clinic BP was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory BP was performed in the final week of each phase. RESULTS: Compared with the placebo phase, end of phase clinic BP was unchanged by any of the progestogen treatments. There was a dose-dependent decrease in ambulatory daytime diastolic and mean arterial BP with the progestogen treatments compared with placebo (P < 0.05). CONCLUSION: In a regimen of postmenopausal hormone replacement therapy with a fixed mid-range daily dose of CEE combined with a cyclical regimen of a C21 progestogen spanning the current clinical dose range, the progestogen has either no effect or a small dose-dependent reduction in clinic and ambulatory BPs over one treatment cycle.