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[A case of postoperative recurrent breast cancer with multiple lung metastases that completely responded to combination therapy of docetaxel (TXT) and medroxyprogesterone acetate (MPA)].

A 54-year-old female had undergone surgery for breast cancer 5 years ago, after which she developed multiple lung metastases, in spite of treatment with various postoperative chemoendocrine therapies. The patient who had recurrent breast cancer with multiple lung metastases was treated with a combination of docetaxel (TXT) 80 mg/body three cycles, two courses of 40 mg/body four times and medroxyprogesterone acetate (MPA) 600 mg p.o. daily. Six months later, the lung metastases had completely disappeared on chest CT-scan. Complete remission has been maintained for one and half years. The use of combined chemoendocrine therapy with TXT and MPA is considered effective for recurrent breast cancer as second-line therapy.

Antineoplastic Combined Chemotherapy Protocols↗

The effects of epirubicin hydrochloride (EPI) plus pretreatment of medroxyprogesterone acetate (MPA) on FM3A breast cancer cells transplanted in female C3H/He mice.

BACKGROUND: Little is known about how breast cancer cells are affected by the different regimens of medroxyprogesterone acetate (MPA) hormone therapy in combination with epirubicin (EPI). MATERIALS AND METHODS: The effectiveness of EPI with and without MPA pretreatment was compared when used on FM3A mouse breast cancer (FM3A) cells transplanted in female C3H/He mice. The effects of these regimens on angiogenesis induced by FM3A tumor were evaluated. RESULTS: A significant enhancement of the effects of EPI on the growth of FM3A cells by continuous MPA treatment was observed. The continuous treatment of MPA with EPI was most effective in the inhibition of angiogenesis in the tumors in all regimens tested. CONCLUSION: The combination of MPA pretreatment with EPI may be more effective than the simultaneous treatment of MPA with EPI for breast cancer. In addition, the results suggest that the anti-angiogenic effects of MPA combined with EPI on FM3A cells are parallel with the anti-tumor effects.

Angiogenesis Inhibitors↗

Effect of depot medroxyprogesterone acetate and testosterone ananthate on the testis of albino rats: ultrastructural and biochemical studies.

Male albino rats were treated with depot medroxyprogesterone acetate (1 mg/animal/day) + testosterone ananthate (100 micrograms/100 g body weight/day) for 30 and 60 days. After 30 days of treatment, all the testicular enzymes like beta-glucuronidase, hyaluronidase, sorbitol dehydrogenase, lactate dehydrogenase, acid and alkaline phosphatase, registered non-significant decrease in their values. Fifty percent of the treated animals achieved sterility after 30 days of treatment. After 60 days of treatment the testis showed degenerative changes in Golgi phase and late spermatids. Changes in the Golgi phase spermatids were related with degeneration of the nuclear membrane. Changes in the late phase spermatids included mitochondrial hypertrophy of the midpieces, membrane lysis, absence of cristae and degeneration of annulus leading to detachment of tail. Cytoplasm of luminal area displayed hypertrophied mitochondria devoid of cristae, prominent appearance of Golgi bodies, intense lysosomal activity and ample vacuolation. Tail fragments of degenerated spermatids prevailed in luminal cytoplasm. Except for beta-glucuronidase which registered a significant decrease, levels of all the other testicular enzymes, viz. hyaluronidase, lactate dehydrogenase, sorbitol dehydrogenase, acid phosphatase and alkaline phosphatase were within their control limits. The ultrastructural and biochemical changes are correlated.

Animals↗

[Plasma estrogen levels in postmenopausal women treated with estrogens alone or combined with medroxyprogesterone acetate in the same tablet].

A study was carried out with 30 postmenopausal women, treated with conjugated estrogens, alone, or associated with medroxyprogesterone acetate in the same tablet, assaying their plasmatic estrogen levels before and during the treatment, besides its clinical efficacy. There were no significative differences of a given doses in neither of both aspects. The conclusion was that the associated hormonal replacement therapy is a good choice that improves patients compliance with the therapy.

Adult↗

[A case of jejunal vein thrombosis due to medroxyprogesterone acetate].

The patient was a 68-year-old woman with advanced breast cancer which had been treated by modified radical mastectomy two years and nine months earlier. After the surgery, tamoxifen citrate (TAM) was orally administered in addition to various types of chemotherapy. Because the patient complained of nausea and weight loss, medroxyprogesterone acetate (MPA) was orally administered instead of TAM. The patient complained of intense abdominal pain on the 35th day of administration. Laparotomy was then performed for her acute abdominal problem. Because necrosis from bleeding due to jejunal vein thrombosis was observed in the jejunum for about 15 cm, resection of the jejunum was carried out. Histological observation demonstrated thrombosis in the vein, and cellular infiltration around the thrombosis. The postoperative prognosis has been favorable and the postoperative course is now being monitored at our clinic (2 months after surgery). The patient has no complications such as diabetes mellitus or hypercholesterolemia. The thrombosis observed in the jejunal vein, which is a rare site for it on the 35th day of MPA administration was induced by MPA. Due attention must be paid to the formation of thrombosis when using MPA.

Administration, Oral↗

Plasma leptin in postmenopausal women with coronary artery disease: effect of transdermal 17beta-estradiol and intermittent medroxyprogesterone acetate.

OBJECTIVES: In the present study, the relationship between plasma leptin and other cardiovascular risk factors in high-risk postmenopausal women was assessed, as well as the effect of transdermal 17beta-estradiol unopposed or in combination with intermittent medroxyprogesterone acetate (MPA) on plasma leptin. METHODS: Postmenopausal women (n = 118) with coronary artery disease (CAD) were consecutively recruited from women admitted to hospital for coronary angiography. They were randomized to estradiol plus intermittent MPA or to a control group, and investigated at study inclusion, and after 3 and 12 months. RESULTS: A strong relationship was found between leptin and body mass index (r = 0.69, p < 0.001). Leptin was related to lipid fractions (high-density lipoprotein cholesterol: r = -0.33, p < 0.001; apolipoprotein A: r = -0.28, p = 0.004; and triglycerides: r = 0.27, p = 0.003) and indices of glucose metabolism (C-peptide: r = 0.47, p < 0.001; fasting insulin: r = 0.42, p < 0.001; glucose: r = 0.25, p = 0.008; insulin resistance: r = 0.45, p < 0.001; and insulin secretion: r = 0.36, p < 0.001). In a multiple regression model, only body mass index (p < 0.001) and C-peptide (p = 0.002) remained as independent factors for leptin levels. Despite the association with sex hormone-binding globulin (r = 0.30, p = 0.001), no effect on leptin levels was observed with either unopposed transdermal estradiol or estradiol combined with MPA. CONCLUSION: Plasma leptin is related to other cardiovascular risk factors in postmenopausal women with CAD, but seems to be unaffected by transdermal 17beta-estradiol administration.

Administration, Cutaneous↗

The in-vitro effects of medroxyprogesterone acetate on acidic pH induced apoptosis of periferal blood mononuclear cells.

Medroxyprogesterone acetate (MPA) which has a steroid structure, is widely used in oncology practice in the treatment of the cachexia of cancer and to reduce hematologic toxicity in patients receiving chemotherapy. However, the mechanisms of MPA on these effects are unclear. In this study, we investigated the effects of two different doses of MPA (10(-5) and 10(-6) M/L) on acidic pH induced apoptosis of periferal blood mononuclear cells (PBMC) derived from 10 healthy volunteers. Compared with the control group, we found that MPA at the dose of 10(-5) M/L had a negative effect on apoptosis (32.88 +/- 4.61 and 20.7 +/- 1.53% respectively, p < 0.05), a positive effect on cell count of PBMC (1395 +/- 151 x 10(3) and 1100 +/- 139 x 10(3) respectively, p < 0.05) and no effects on cell viability and its proliferation. More comprehensive trials are needed to clarify this effect of MPA.

Adult↗

[Effect of injection of testosterone undecanoate and depot medroxyprogesterone acetate on the suppression of spermatogenesis].

OBJECTIVE: To observe depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-week intervals for the suppression of spermatogenesis in healthy Chinese men. METHODS: After 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. RESULTS: Consistent 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. CONCLUSION: The lower combined dosage is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.

Adult↗

Cystic endometrial hyperplasia and endometritis in a dog following prolonged treatment of medroxyprogesterone acetate.

An 8-year-old female Yorkshire Terrier was presented for investigation of reduced appetite, and occasional vomiting. She has been treated with medroxyprogesterone acetate (MPA) from past 3 year-old age for contraception. Abdominal sonography showed abnormal enlargement of uterus, and ovariohysterectomy was performed. Main gross findings of uterus were enlarged lesions in two areas of the left horn, which had thickened wall and yellowish sticky material in the lumen. Histopathologically, cystic endometrial hyperplasia (CEH) and endometritis were present in the thickened area. In this case, CEH and endometritis may be attributed to prolonged treatment of MPA. It was concluded that further study is needed to clarify the association of MPA treatment with age, its pathogenesis and abnormal uterine changes in dogs.

Animals↗

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.

Adolescent↗

[Two cases of advanced breast cancer responding to oral chemoendocrine therapy with 5'-deoxy-5-fluorouridine, medroxyprogesterone acetate and cyclophosphamide (DMpC)].

Two patients were diagnosed as advanced breast cancer with multiple bone metastases. DMpC therapy (oral chemoendocrine combination therapy with doxifluridine, medroxyprogesterone acetate and cyclophosphamide) was chosen as first-line chemotherapy. After one month of the treatment, reductions in the primary tumors, lymph node metastases and metastatic bone lesions were noted. Only grade 2 leukopenia was observed as an adverse event in only one patient. DMpC therapy is an effective, easy and safe oral therapy. Therefore, it is possible to continue medication on an ambulatory basis for the long-term. DMpC therapy could thus be one the most useful treatments for advanced breast cancer.

Administration, Oral↗

[A case of anthracycline and taxane-resistant breast cancer with life-thereatening multiple liver metastases responding to oral combination chemotherapy by UFT, cyclophosphamide and medroxyprogesterone acetate].

A 53-year-old woman presented with an advanced right breast cancer together with skin manifestations and massive axillary lymph node metastases, as well as distant metastases in the lung and the liver. The patient received surgery after 6 courses of chemotherapy with epirubicine and intravenous cyclophosphamide (80/600 mg/m2). A weekly paclitaxel regimen (80 mg/m2) was started because the tumor markers increased soon after surgery. Despite chemotherapy, no response was confirmed, then weekly docetaxel (35 mg/m2) was started. Although the tumor markers decreased after administration of docetaxel, severe liver disfunction appeared and did not improve after cessation of docetaxel. Computed tomography (CT) revealed numerous metastatic nodules in the bilateral lobes of the liver. UFT (400 mg/day) and cyclophosphamide (100 mg/day) were administered for 4 weeks followed by 2 weeks cessation and then combined with continuous medroxyprogesterone acetate (800 mg/day). Liver function tests were normalized 3 months after, and the massive metastatic liver tumors disappeared completely. Lung metastasis also subsided. In spite of these good responses, tumor markers did not normalize and skin nodules appeared around the surgical site. Administration was stopped 36 weeks after initiation of the treatment.

Adenocarcinoma, Scirrhous↗

Bone loss associated with long-term use of depot medroxyprogesterone acetate.

On 17 November 2004, the United States Food and Drug Administration issued a black box warning on the long-term use of depot medroxyprogesterone acetate stating that bone loss might be irreversible with use of more than 2 years. Despite the seriousness of such a safety warning, the Food and Drug Administration provided no clinical recommendations. Various professional bodies have made different recommendations on the management of women prescribing such long-term injections but there is no consensus on the best practice. Thus individual institutions need to revise service protocols. The Health Services Subcommittee of the Family Planning Association of Hong Kong has reviewed the scientific evidence from international and local studies and made its recommendations in a meeting held on 1 March 2005. This article aimed to share our opinion with other medical professionals in Hong Kong.

Adolescent↗

Medroxyprogesterone acetate stimulates cdk inhibitors, p21 and p27, in endometrial carcinoma cells transfected with progesterone receptor-B cDNA.

PURPOSE OF INVESTIGATION: Progestin is reported to suppress the growth of endometrial carcinomas, although its precise mechanism of action is not clear. This study aimed to transfect progesterone receptor-B (PRB) cDNA into endometrial carcinoma cells and investigate the effect of medroxyprogesterone acetate (MPA) on cell growth, and p21 and p27 expression in the transfectant. METHODS: Immunoblotting for p21 and p27 was performed at predetermined times after the administration of MPA. RESULTS: PR expression was maximally induced in Ishikawa cells at 24 hrs after the transfection. At 1 x 10(-6) M, MPA suppressed the growth of the transfectant by 34% on day 6 and stimulated p21 accumulation at 48 to 72 hrs and p27 accumulation at 48 to 96 hrs after its administration. PRB cDNA was effectively transfected and in the transfectant MPA at 1 x 10(-6) M, the dosage suppressing growth, induced p21 and p27expression. CONCLUSION: p21 and p27 may be related to progesterone-induced growth suppression in human endometrial adenocarcinoma.

Blotting, Western↗

The use of medroxyprogesterone acetate for the treatment of sexually inappropriate behaviour in patients with dementia.

Sexually inappropriate behaviour in a patient with dementia can be a problem for caregivers. Little research has been done concerning treatment for this behavioural disorder. The hormone medroxyprogesterone acetate (MPA) is a known, but infrequently used, treatment option. We describe a series of 5 cases in which MPA was used successfully to control inappropriate sexual behaviours in men with dementia.

Aged↗

[Cyclic ethinyl estradiol and medroxyprogesterone in climacteric women. Their clinicAL efficacy and patterns of uterine bleeding].

The study evaluated the clinical efficacy substitutive hormonotherapy regime in a group of 40 postmenopausal, women with moderate to severe symptomatology and negative progesterone challenge test. Each cycle consisted in the administration of 15 micrograms of ethinyl estradiol during 21 days, plus 10 mg medroxyprogesterone acetate (MPA) the last 10 days. Each patient received four cycles of therapy with 10 days of interval between them. The global clinical response was evaluated as favorable (excellent and good responses) in 97.5% of the patients. All the patients showed an improvement of the vaginal trophism (colpocytology). The great majority of the women experimented cyclical bleeding as consequence of the treatment. The post-therapeutic bleeding (Withdrawal) was the predominant bleeding pattern. This fact suggests that the 10 mg of MPA added daily during 10 days could allow a suitable opposition to the estrogenic proliferative effect inducing an adequate secretory response and the subsequent endometrial desquamation.

Climacteric↗

Antitumor effect of lonidamine alone or combined with tamoxifen or medroxyprogesterone acetate in breast cancer cells.

The effect of Lonidamine (LND) alone or combined with the antiestrogen Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) on cell proliferation and steroid hormone receptor content of a human estrogen sensitive breast cancer cell line was investigated. LND has a direct growth inhibitory action, even if used at relatively low concentrations (10(-7) M), and shows the maximum effect at 10(-4) M. The combination of LND with the antiestrogen does not produce a potentiation of the TAM-induced reduction of cell number, while the association of the drug with MPA seems more effective with respect to MPA alone, at least at certain concentrations. The negative interference observed between LND and TAM may be due to the LND-induced decrease of estrogen receptor levels.

Antineoplastic Combined Chemotherapy Protocols↗

Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity.

The incidence of perforation and deep ulceration of the alkali-burned rabbit cornea was substantially reduced by topical or parenteral administration of medroxyprogesterone. The mode of action of the hormone is probably at least in part related to its suppressive effects on production of tissue collagenase, as indicated by the considerable reduction in collagenolytic activity by living explants of the treated corneas.

Alkalies↗