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PubMed2005

Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.

BACKGROUND: Several studies report an association between depot medroxyprogesterone acetate (DMPA) injectable contraception and decreased bone mineral density. Adolescents, who are still gaining bone, may be particularly affected, but there has been little study of the association in adolescent users and none following discontinuation. OBJECTIVE: To evaluate bone mineral density changes in adolescents using and discontinuing use of DMPA contraception. DESIGN: A population-based prospective cohort study. PARTICIPANTS: One hundred seventy adolescent women, aged 14 to 18 years; 80 baseline DMPA users and 90 age-similar, unexposed comparison women. Sixty-one participants discontinued DMPA use during follow-up. MAIN OUTCOME MEASURE: Bone mineral density, measured every 6 months for 24 to 36 months at the hip, spine, and whole body, comparing mean bone mineral density changes in DMPA users and discontinuers with nonusers. RESULTS: Among DMPA users, bone mineral density declined significantly relative to nonusers at the hip and spine but not the whole body. Annualized mean percentage changes, adjusted for covariates, were hip, -1.81% vs -0.19%; P<.001; spine, -0.97% vs 1.32%; P<.001, and whole body, 0.73% vs 0.88%; P = .78 for DMPA users vs nonusers, respectively. New users lost bone mineral density more rapidly than prevalent users. Discontinuers experienced significantly increased bone mineral density relative to nonusers at all anatomical sites; annualized mean percentage changes were hip, 1.34% vs -0.19%; P = .004; spine, 2.86% vs 1.32%; P = .004; and whole body, 3.56% vs 0.88%; P<.001. CONCLUSIONS: Use of DMPA contraception in adolescents was associated with significant continuous losses of bone mineral density at the hip and spine. However, significant gains postdiscontinuation provide evidence that the loss of bone mass is apparently reversed.

Absorptiometry, Photon↗
PubMed2006

Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method.

OBJECTIVE: To examine weight changes in a large cohort of obese and nonobese adolescent girls initiating depot medroxyprogesterone acetate (DMPA), an oral contraceptive (OC), or no hormonal contraceptive method (control). DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 450 adolescent girls, aged 12 to 18 years, who attended 4 urban health clinics and selected DMPA, OC, or control. Data collection occurred at baseline and at 6, 12, and 18 months; consisted of structured interview and measurement of height and weight; and occurred from April 19, 2000, through September 26, 2003. MAIN OUTCOME MEASURE: Weight was examined as mean change over 18 months and actual weight at each study visit. On the basis of preliminary analyses, we stratified the sample according to baseline obesity status (nonobese, body mass index [calculated as weight in kilograms divided by the square of height in meters] < 30; obese, body mass index > or =30). RESULTS: Adolescent girls who were obese at initiation of DMPA gained significantly more weight than did obese girls starting OC or control (P<.001 for both). At 18 months, mean weight gain was 9.4, 0.2, and 3.1 kg for obese girls receiving DMPA, receiving OC, and control, respectively. Weight gain in obese girls receiving DMPA was also greater than weight gain in all nonobese categories (4.0 kg, DMPA; 2.8 kg, OC; 3.5 kg, control; P<.001). A significant interaction (P = .006) between length of time receiving DMPA and weight gain was evident for obese subjects. CONCLUSIONS: Over 18 months, DMPA use was associated with increasing rates of weight gain in obese subjects. The potential contribution to severe obesity in this population is concerning.

Adolescent↗
PubMed1981

Medroxyprogesterone therapy for sexual precocity in girls.

An evaluation of 13 girls who had been treated intramuscularly with medroxyprogesterone acetate for sexual precocity showed that this drug has no effect on growth, skeletal maturation, or adult height. During treatment (mean duration, 3.6 years), menstruation was suppressed and breast size initially regressed, but breast development and public hair development progressed during long-term therapy. The extent of delay in resumption of menses after cessation of therapy was related both to duration of treatment and dosage of the drug.

Body Height↗
PubMed1995

Depot medroxyprogesterone acetate and breast cancer. A pooled analysis of the World Health Organization and New Zealand studies.

BACKGROUND: Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. DESIGN: Pooled results from two case-control studies. SETTING: New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). PARTICIPANTS: A total of 1768 women with breast cancer and 13,905 controls, most of whom were younger than 55 years. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer in women who had used DMPA. RESULTS: The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). CONCLUSIONS: The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use.

Adolescent↗
PubMedDate not supplied

Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women.

CONTEXT: Lower-than-commonly-prescribed doses of conjugated equine estrogens (CEEs) with medroxyprogesterone acetate (MPA) improve vasomotor symptoms and vaginal atrophy, provide acceptable bleeding and lipid profiles, and afford endometrial protection. This lower-dose therapy's protection against loss of bone mineral density (BMD) associated with menopause has not been thoroughly investigated. OBJECTIVE: To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD, total body bone mineral content (BMC), and biochemical markers of bone turnover in postmenopausal women. DESIGN AND SETTING: Two-year randomized, double-blind, placebo-controlled substudy of the Women's Health, Osteoporosis, Progestin, Estrogen trial, conducted at 19 US centers between August 1995 and October 2000. PARTICIPANTS: Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period. INTERVENTIONS: Patients were randomly assigned to receive CEEs, 0.625; CEEs, 0.625 and MPA, 2.5; CEEs, 0.45; CEEs, 0.45 and MPA, 2.5; CEEs, 0.45 and MPA, 1.5; CEEs, 0.3; CEEs 0.3 and MPA, 1.5 (all doses in mg/d); or placebo for 2 years. All participants also received elemental calcium at 600 mg/d. MAIN OUTCOME MEASURES: Changes from baseline in spine and total hip BMD, total body BMC, and biochemical markers of bone turnover (serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen), assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach. RESULTS: At 24 months, women assigned to all of the active treatment groups had significant gains from baseline (P<.001) in spine and hip BMD and total body BMC (except total body BMC in the group receiving CEEs, 0.3 mg/d). These changes were significantly different from those in the placebo group, in which losses of bone mass in spine and total body were evident over the course of the study (P<.001). The loss in hip BMD from baseline in the placebo group was significant at 18 (P =.02) but not at 24 months (P =.06). Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline (P<.001) for all active treatment groups at all time points; no changes were found for the placebo group. For women treated with CEEs alone, the gains in spine BMD for the group taking CEEs, 0.625 mg/d, were significantly higher than those of the group taking CEEs, 0.3 mg/d (P =.02), but not the group treated with CEEs, 0.45 mg/d (P =.48). CONCLUSIONS: Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women.

Adult↗
PubMed1997

Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats.

The novel anti-estrogen EM-800 and medroxyprogesterone acetate (MPA) inhibit estrone (E1)-stimulated growth of dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in a rat model. After 65 days, ovariectomy (OVX) decreased total tumor area to 9.6 +/- 3.9% of initial size, while E1 (1.0 microg, s.c., twice daily) stimulated tumor growth to 225 +/- 40.9% of initial size. Daily oral administration of 2.5 mg/kg body weight of EM-800 completely abolished E1-stimulated tumor growth. A low daily dose of EM-800 (0.25 mg/kg body weight) or MPA (1 mg, s.c., twice daily) used alone partially reversed the stimulatory effect of E1 on the growth of DMBA-induced tumors. The combination of both compounds, however, caused a more potent inhibitory effect than each compound used alone. A high dose of EM-800 completely or almost completely inhibited the E1-stimulated vaginal and uterine weights, respectively. The same dose of EM-800 completely reversed the inhibitory effect of E1 on serum luteinizing hormone levels. Uterine, vaginal and tumoral estrogen and progesterone receptor levels were reduced markedly following treatment with EM-800. Our data show that the combination of the pure anti-estrogen EM-800 with the androgenic compound MPA achieves greater inhibition of the growth of DMBA-induced mammary carcinoma than that achieved by each compound used alone.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Pharmacokinetics of 9alpha-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity.

Administration, Oral↗
PubMed1977

Combination chemotherapy of germ cell tumors of the testis with vincristine, adriamycin, cyclophosphamide, actinomycin D and medroxyprogesterone acetate.

Forty-three patients with disseminated germ cell cancer were treated with a combination of vincristine, Adriamycin, cyclophosphamide, actinomycin-D, and medroxyprogesterone acetate. All the 43 patients were considered evaluable for response. Thirty-one patients (72%) achieved a complete or partial remission and 14 (32.5%) achieved a complete remission. The patients who attained an objective response obtained a significant prolongation of life compared with the nonresponders (median survival 55 vs. 23 weeks). Responses were seen in all histologic categories and most frequently in patients with metastases confined to the lungs. The major side effects were leukopenia and stomatitis. There were no deaths related to toxicity of the chemotherapy.

Adolescent↗
PubMed1984

Radiosensitizing effect of medroxyprogesterone acetate on endometrial cancer cells in vitro.

From clinical experience it is known that medroxyprogesterone acetate (MPA) can increase the radiosensitivity of adenocarcinomas of the corpus uteri. This study investigates this phenomenon in vitro. Primary explants of highly differentiated adenocarcinomas were irradiated with or without pretreatment with MPA and compared with an untreated control group and to a group treated with MPA only. Cell culture itself was performed on an agarose medium in order to prevent overgrowth by fibroblasts. Untreated samples formed 43 +/- 5 clones, explants treated with MPA only produced 39 +/- 5 clones, a difference which was not statistically different; samples irradiated without pretreatment produced 16 +/- 8 and samples after combined treatment 9 +/- 3 clones (all values means +/- SD). This numeric reduction of cell growth through preirradiation treatment with MPA was statistically significant. The effect of MPA as a radiosensitizer may be due to its potential to prolong the radiosensitive G2 phase of the cell cycle. This effect of MPA may be useful also in other hormone-dependent tumors.

Adenocarcinoma↗
PubMed1985

A randomized comparative trial of combined versus alternating therapy with cytostatic drugs and high-dose medroxyprogesteron acetate in advanced breast cancer.

A prospective multicenter trial was conducted in 155 consecutive patients with Stage IV breast cancer randomly allocated to receive either (1) vincristin (V) 1.2 mg/m2 (maximum dose, 2 mg), Adriamycin (A) (doxorubicin) 40 mg/m2, and cyclophosphamide (C) 500 mg/m2, all intravenously on day 1, every 4 weeks, in combination with medroxyprogesteron acetate (MPA) 600 mg orally on days 1 through 14, 500 mg intramuscularly on days 1 through 28, and twice weekly afterwards (combined chemoendocrine approach) or (2) the same combination chemotherapy (VAC) for three cycles alternating with MPA in the above-mentioned dosage during 8 weeks (alternating chemoendocrine approach). Results show an overall response rate of 73% with 26% complete responses in the combined treatment arm, whereas in the alternating arm, an overall response rate of 76% with 20% complete responses was observed. In patients with more than one metastatic site, response rate was higher in the combination treatment, and only in this arm were complete responses observed in these patients. Although the median duration of response was long in both treatment arms (combination, 19 months versus alternating, 21 months), the median overall survival in both groups was not definitely prolonged (22 versus 24 months, respectively). However, results in subsets of patients suggest that the alternating chemoendocrine approach may be better for estrogen receptor (ER)-negative patients, for patients younger than 51 years of age, and for patients with a disease-free interval of 1 year or less. Patients with these parameters probably belong to the same population. It is concluded that combination of chemotherapy and high-dose MPA may be indicated in ER-positive patients when a clinical response is urgently needed. In ER-negative patients, the alternating use of both treatment modalities deserves further investigation.

Aged↗
PubMed1994

Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration for endometrial hyperplasias.

BACKGROUND: To determine the biologic difference between normal endometrium and endometrial hyperplasias, the authors assessed the expression of estrogen receptors (ER) and progesterone receptors (PR) in the subjects before and after oral administration of medroxyprogesterone acetate (MPA) (Hysron-H, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan). METHODS: The authors studied the expression of ER and PR in pathologic conditions of the endometrium such as cystic, adenomatous, and atypical hyperplasias before and after MPA treatment, 600 mg daily, for 8-14 weeks, and compared this expression with that of normal endometrium. RESULTS: Stromal and epithelial components of the normal endometrium in the proliferative phase were positive for ER and PR. In the secretory phase and after MPA treatment, the epithelial component showed either negative or faint staining for ER and PR, but the stromal component showed positive staining for PR and negative or faint staining for ER. All hyperplasias exhibited ER and PR in the stromal and epithelial components, although the intensity of the staining was variable in atypical hyperplasias. After MPA treatment, in the epithelial component of cystic and adenomatous hyperplasias, down-regulation of PR was prominent, but many cells continued to express ER. The epithelial component usually was surrounded by PR-positive decidual cells. In atypical hyperplasia, many cells continued to express ER and PR in the epithelial component surrounded by both ER and PR positive stromal cells after MPA treatment. CONCLUSIONS: Among the pathologic conditions of the endometrium, cystic and adenomatous hyperplasias have mechanisms of down-regulation of PR but not ER in the glandular component after MPA treatment, whereas in atypical hyperplasia, down-regulation of ER and PR does not occur in the epithelial component. Compared with normal endometrium, the majority of endometrial hyperplasias have an impairment of down-regulation of ER in the epithelial component by MPA treatment, and atypical hyperplasia has an impairment of down-regulation of ER and PR. Endometrial hyperplasias seem to have an abnormality of down-regulatory mechanisms of sex steroid receptors in the epithelial component when treated with exogenous progesterone.

Adult↗
PubMed2000

Cytologic findings in cervical smears in patients using intramuscular medroxyprogesterone acetate (Depo-provera) for contraception.

The purpose of the present study was to assess the findings in cervical smears associated with intramuscular depot medroxyprogesterone acetate (Depo-Provera) contraception. Seventy-four cervical smears of reproductive-age patients on Depo-Provera were reviewed for cytologic abnormalities, predominant cell type, and intermediate cell glycogenation (extensive (EGly) = navicular cells / glycogenation in 10 or more high-powered fields (hpf); moderate (MGly) = 5-10 hpf; and focal (FGly) = less than 5 hpf). A control group of 38 nonpregnant patients without hormonal therapy was reviewed. Study group patients' (SGP) age ranged from 16-44 years (average 28.1); control group patients (CGP) from 17-42 years (average 29.4). Time since last menstrual period (LMP) for the SGP was 16.9 months (range 1-96); LMP for CGP was 18.2 days (range 5-33). Four (5.4%) SGP had squamous intraepithelial lesions (SIL), four (5.4%) atypical squamous cells of undetermined significance (ASCUS), and one (1.4%) atypical repair. No CGP had SIL or ASCUS. Seventy-three (98.6%) SGP had intermediate cell (IC) predominance; one had parabasal cell predominance. Of the CGP, 28 (73.7%) had IC predominance, nine (23.7%) superficial cell (SC) predominance and one (2.6%) had near equal IC and SC. EGly was seen in 22 (29.7%) SGP; two (5.3%) in CGP (chi-square 7.53; 0.95 = 3.84). MGly was seen in 29 (39.2%) SGP; 10 (26.3%) in CG. FGly was seen in 17 (22.9%) SGP; 14 (36.8%) in CGP. No glycogenation was seen in six (8.1%) SGP; 12 (31.6%) in CGP. Time since LMP was inversely proportional to glycogenation in SGP: EGly-LMP 11.6 months; MGly-LMP 14.9 months; FGly-LMP 15.0 months; and no glycogenation-LMP 22.5 months. Glycogenation of IC appears inversely proportional to Depo-Provera effect. EGly due to recent Depo-Provera administration mimics changes associated with pregnancy.

Adolescent↗
PubMed1993

Apical excrescences in the gallbladder epithelium of the female Syrian hamster in response to medroxyprogesterone.

All the intact female Syrian hamsters treated with medroxyprogesterone (MP) for a one-month period, without dietary manipulation, display gallbladder surface epithelial changes, and intraluminal deposits. These changes include excrescences in various stages, bulging, and extrusion of material from the epithelial cells. The most striking scanning electron microscopic observations are the dramatic events, comparable to apocrine-like secretory events observed in another related study using oophorectomized hamsters. Since the hamster gallbladder does not possess mucous goblet cells, it appears that this phenomenon could be a response to the MP treatment, thus providing a larger amount of mucous product than usual with cellular material, in addition to the possible alteration in the quality of the bile following this treatment. As a result of MP treatment, intraluminal deposits were also confirmed by using light and transmission electron microscopy. In control hamsters these events were not observed, however, small blebs outlining surface epithelial cells are seen. The results in this report complement the previous studies using the male and oophorectomized Syrian hamster model subjected to similar experimental conditions.

Animals↗
PubMed1993

Pharmacokinetics and bioavailability of medroxyprogesterone acetate in the dog and the rat.

Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and 10 mg MPA and a single intravenous dose of 1 mg MPA. Rats received single oral doses of 0.2, 1, 5, and 20 mg kg-1 MPA and multiple oral doses (14 daily doses) of 0.2, 5, and 20 mg kg-1 MPA. Dog plasma MPA levels from the intravenous dose were characterized by a triexponential decay with disposition half-lives of 0.3, 1.8, and 21.6 h. A Loo-Riegelman analysis of the dog plasma MPA levels from oral doses indicated absorption was not a simple first-order process. The Weibull Function was used to characterize the absorption kinetics of MPA. The oral absorption of MPA in dogs appears to be dose-linear over the dosage range studied, and the absolute bioavailability was estimated at 27 per cent. Rat plasma MPA levels from single and multiple oral doses were analyzed by a non-compartmental approach. AUC and Cmax values were not dose-linear over the dosage range studied; indicative of the self-induced metabolism of MPA. Exposure of similar dosages of MPA to both the rat and the dog resulted in similar plasma profiles and pharmacokinetics.

Administration, Oral↗
PubMed2006

Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate.

BACKGROUND: Menorrhagia is a serious complication in young female oncology patients who suffer from severe thrombocytopenia during myelosuppressive treatment. To the authors' knowledge, little is known regarding the incidence of this complication or the effectiveness of possible therapies for its prevention. METHODS: In this retrospective clinical study, after a thorough gynecologic evaluation, young female oncology patients with regular menstrual cycles undergoing myelosuppressive treatments received either depo-medroxyprogesterone acetate (DMPA), or D-tryptophan-6-luteinizing hormone-releasing hormone depot treatment (gonadotropin-releasing hormone agonist [GnRH-a]), or no treatment before the administration of myelosuppresive chemotherapy. Only patients who later developed severe thrombocytopenia (<25,000 platelets per muL) were included in the study. Daily blood counts, menorrhagia, nonvaginal bleeding episodes, and the need for blood products, gynecologic consultations, and other medical interventions were determined. RESULTS: Of 101 women with cancer who met the inclusion criteria, 42 patients received DMPA, 39 patients received GnRH-a, and 20 patients remained untreated. The mean duration (+/- standard deviation) of severe thrombocytopenia was 24.76 +/- 23.6 days. Four patients were not included because of significant gynecologic pathologies. General bleeding from nongynecologic sites was similar for all groups and was not associated with vaginal bleeding. Severe or moderate menorrhagia was documented in none of the 39 women who received GnRH-a, in 9 patients (21.4%) who received DMPA, and in 9 untreated patients (40%; P = .02). Fewer calls for urgent gynecologic consultations were documented in the GnRH-a group compared with the untreated group (P < .0001). CONCLUSIONS: Female patients undergoing myelosupressive therapy are at high risk of developing significant menorrhagia during prolonged, severe thrombocytopenia. Pretreatment gynecologic evaluation can detect significant pelvic pathologies. GnRH-a treatment effectively prevented menorrhagia, whereas DMPA administration was less effective.

Adolescent↗
PubMed1994

Angiostatic activities of medroxyprogesterone acetate and its analogues.

The effects of medroxyprogesterone acetate (MPA) (I) and related compounds (II-VI) upon angiogenesis induced by basic fibroblast growth factor (bFGF) or transforming growth factor-alpha (TGF-alpha) were investigated using a rabbit corneal system for assay of angiogenesis. Dexamethasone (Dex) was used as a positive control. The MPA analogues tested were 6,6'-dehydro-MPA (II), megestrol acetate (III), 1-dehydromegestrol acetate (IV), melengestrol acetate (V), and 1-dehydromelengestrol acetate (VI). The inhibitory activities of these steroids using bFGF were in the order: Dex = MPA = (VI) = (V) > (IV) > (III). Steroid (II) was inactive. 5 alpha-dihydrotestosterone was weakly active, while estradiol-17 beta and progesterone were inactive. The angiostatic activity of MPA was completely abolished by mefipristone (RU 486) which showed no anti-angiogenic activity in this assay. With TGF-alpha, the order of angiostatic activities was Dex = (VI) > (IV) > (III) > (V). Steroid (II) was again inactive. Dex, MPA, and all the MPA analogues except steroid (II) markedly inhibited the activity of plasminogen activator secreted by cultured calf pulmonary artery endothelial cells, but did not inhibit growth of these cells. The binding affinities of MPA and its analogues to glucocorticoid, progesterone and androgen receptors were determined, but were found not to be correlated with their angiostatic activities.

Animals↗
PubMed1994

Effect of sialoadenectomy on medroxyprogesterone-acetate-induced mammary carcinogenesis in BALB/c mice. Correlation between histology and epidermal-growth-factor receptor content.

To evaluate the possible involvement of the salivary glands in the modulation of medroxyprogesterone (MPA)-induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were treated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumors developed in 11 sialoadenectomized and in 34 control mice with similar latencies. In both groups, 75% of the tumors were ductal and progestin-dependent (PD) while the remainder were lobular and progestin-independent (PI). Epidermal growth factor (EGF) levels were measured in salivary glands (SG-EGF) and serum (S-EGF) in both groups. MPA induced a significant increase in SG-EGF and in S-EGF that became evident only after 1 month of MPA treatment. No increase in S-EGF was detected in MPA-treated sialoadenectomized mice, indicating that salivary glands are the major source of S-EGF. The presence of EGF receptors (EGF-R) was investigated in ductal PD and PI tumor lines and compared with 8 PI tumor lines of lobular origin. A significant difference in EGF-R content was found between lobular and ductal tumors. No increase in EGF-R was noted when ductal tumors became autonomous. EGF-R did not correlate with tumor growth rate and there was an inverse correlation between EGF-R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, 1 ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found to be significant when compared with the controls. It may be concluded that SG-EGF plays an important role in the induction of mammary adenocarcinomas by MPA, while it has no significant effect on the growth of established tumors.

Animals↗
PubMedDate not supplied

International forum update: depot medroxyprogesterone acetate and endometrial carcinoma.

In response to a recent report (Fam Plann Perspect 11: 47, 1979) that two of 12 rhesus monkeys given 50 times the human dose of depot medroxyprogesterone acetate (DMPA), by body weight, for ten years had developed endometrial carcinoma (CA), a retrospective survey of all hospital admissions for proven endometrial CA in two Thai provinces where DMPA contraceptive injections have been widely used since 1965 was made. From 1974 through 1978, 16 women were hospitalized with confirmed diagnoses of endometrial CA. None of the nine women successfully followed up had previously used oral or injectable contraceptives, nor has the recorded incidence of endometrial CA increased in these provinces. Base on the available evidence, the authors conclude that (a) the data on monkeys given very large doses of DMPA for ten years do not apply to women given normal doses of DMPA for prolonged periods and (b) widespread and long-term use of DMPA can and should be continued.

Adult↗