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[An introductory clinical trial of three-monthly injectable contraceptive-depot medroxyprogesterone acetate].

OBJECTIVE: To evaluate contraceptive efficacy, continuative rate of use, side effects and acceptability of depot medroxyprogesterone acetate (DMPA) injectable contraception preparation in Chinese women. METHOD: This was an open study. One thousand nine hundred and eighty-five women acquiring contraception received DMPA injection after obtaining informed consent and were followed-up every 3-month up to one year. RESULTS: The total experience accumulated was 1,731.7 women-year with DMPA for 1,985 users. The one year continuation rate was 77.4%. Three subjects became pregnant, the one year accumulative life table failure rate was 0.2%. The accumulative discontinuation rates at one year for other reasons were amenorrhoea (4.8%), bleeding related (13.4%), other medical reasons (2.6%), other personal reasons (2.1%) and lost to follow-up (1.6%). The main complaints were irregular bleeding, amenorrhoea and prolonged bleeding. Lactating women had significantly lower rate of complaint. CONCLUSION: DMPA is a highly effective long-acting contraceptive, it could have good acceptability, especially for lactating women, under the well consultation.

Adolescent↗

Treatment of endometriosis with depot medroxyprogesterone acetate: a preliminary experience.

The efficacy of depot medroxyprogesterone acetate in the treatment of endometriosis was assessed in 19 patients with severe diseases. Assessment was based on changes in subjective symptoms and signs at 4 weekly interval during treatment and after 52 weeks follow up, and changes in visible deposits and adhesions at laparoscopy before and after treatment. There were significant reductions in mean total subjective and symptoms scores, mean total R-AFS adhesions and implants scores, and mean additive diameter of implant scores at the end of treatment and follow up. Treatment success occurred in 75% of the patients, majority (66%) of whom had complete resolution of deposits. Side effects encountered include menorrhagia, break through bleeding, excessive weight gain, myalgia, breast pain, acne and delay in return of menses. It was concluded that DMPA an effective, cheap and readily available medication which is worth using in patients who can not afford the expensive alternatives.

Acne Vulgaris↗

[Evaluation of safety in Chinese women with amenorrhea following injection of depot-medroxyprogesterone for contraception].

OBJECTIVE: To determine whether serum estradiol (E2) level was low after Depot-medroxyprogesterone (DMPA) induced amenorrhea for contraception, thus to evaluate the safety of using DMPA. METHODS: Forty four Chinese women with amenorrhea after injecting DMPA were investigated, and the median period of amenorrhea was 18 months. Symptoms, pelvic examination, serum E2 and follicular stimulating hormone (FSH) levels, and vaginal cytology were examined. RESULTS: Women with amenorrhea had neither symptoms nor genital atrophy that similar to menopausal syndrome. The median level of serum E2 was 150.5 pmol/L (equal to the level of early follicular phase), and the median level of serum FSH was 14.0 IU/L. There were no correlation between E2 and FSH levels, and no correlation between amenorrhea period and E2 or FSH levels (P > 0.05) as well. No significant relationship between estrogen effects by vaginal cytology and the time period of amenorrhea was found. However, the estrogen effect was significantly correlated to the interval from last injection to vaginal smear tested. CONCLUSION: It could be concluded that though DMPA may induce amenorrhea, it will not lower serum E2 levels, and the inhibition of ovarian function is reversible.

Adult↗

[Effects of estradiol and medroxyprogesterone on the growth and doxorubin-resistance of drug-resistant human epithelial ovarian cancer cell line OVCAR-3].

OBJECTIVE: To study the effects of estradiol (E2) and medroxyprogesterone acetate (MPA) on the growth of drug resistant human epithelial ovarian cancer cell line. METHODS: OVCAR-3 cells, treated by different concentrations of E2, MPA and verapamil, were examined for their growth inhibitions with methyl thiazolyl tetrazolium (MTT, a tetrazolium dye) rapid photocolorimetric assay. RESULTS: OVCAR-3 cell growth was inhibited by E2 at high concentrations (10.00-100.00 mumol/L) and by MPA at 100.00 mumol/L, while lower concentrations of E2 (0.01-1.00 mumol/L) and MPA (0.01-10.00 mumol/L) had no effect on OVCAR-3 cell growth, neither stimulation nor inhibition. The effect of E2 combined with MPA was more obvious than either one used separately. E2 and MPA in combination with doxorubin showed a synergistic inhibition effect on OVCAR-3 cell growth, which suggested that both of them could reverse the doxorubin resistance of OVCAR-3 cell line. The inhibition effect of Verapamil combined with doxorubin was obviously weaker than that of E2 and MPA. CONCLUSIONS: E2 and MPA could reverse the doxorubin resistance of OVCAR-3 cell line and their inhibition were more obvious than that of verapamil, which suggested that E2 and MPA may be used clinically for adjuvant chemotherapy.

Cell Division↗

Efficacy and acceptability of depo-medroxyprogesterone acetate injection. As a method of contraception in Saudi Arabia.

OBJECTIVE: To determine the efficacy and acceptability of Depo-Medroxyprogesterone acetate (depo-provera) among the women using that method of contraception at King Faisal Military Hospital in the south-west region of Saudi Arabia. METHODS: A preliminary retrospective and questionnaire analysis of 165 Saudi women who had depo-provera as a method of contraception at the contraception clinic of King Faisal Military Hospital over a period of 2 months. RESULTS: The mean age of the women was 31.21 years and the mean parity 6.77. There was no pregnancy reported during the period of use of the contraceptive method which ranged from 3 months to 7.25 years. The side effects were mainly irregular spotting (69%), continuous bleeding per vaginam (7%), amenorrhoea (8%) and menorrhagia (1%). The rest reported normal menstrual pattern. Irregular spotting was common in women who had used the method for less than 2 years while amenorrhoea was the most common menstrual abnormality after 3 years of use. The other complaints included weight gain, loss of hair, abdominal pain and backache. The side effects were not acceptable to 4% of the women and they tried other methods of contraception. Thirteen percent of the women became pregnant after stopping the injections within intervals varying between 6 months to 2 years. Seventeen percent were using the method for the 2nd time. CONCLUSION: Depo-provera is a very effective form of contraception in our community. While a few of the patients (4%) in our series would try other methods if not happy with the side effects, the majority were prepared to cope with the side effects as long as the desired prevention of pregnancy was guaranteed. Further studies are needed to validate these findings.

Abdominal Pain↗

The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment.

OBJECTIVE: Little is known on the type of progestin and regimen type in relation to breast cancer risk. We have compared the effect of medroxyprogesterone acetate (MPA) and norethisterone (NET) on the estradiol stimulated proliferation in MCF-7 cells with respect to different regimens used in combined hormone replacement therapy (HRT). DESIGN: To approximate the in vivo conditions in HRT, MCF-7 cultures were pretreated with estradiol followed by estradiol/progestin treatment to represent the sequential combined model and compared with non pretreated cultures followed by estradiol/progestin treatment for the continuous combined model. RESULTS: When using progestins in the continuous combined form with estradiol (10(-10) M) both progestins showed a significant reduction in the estradiol stimulated proliferation of the MCF-7 cells. In the sequential combined model the addition of MPA led to a stronger significant reduction of MCF-7 proliferation but in a narrower concentration range (from 10(-8) to 10(-6) M) compared to the continuous treatment. NET did not show any significant effect on proliferation in the SC model. CONCLUSION: Different regimen types and different progestins do lead to significantly different effects on the proliferation of a breast cancer cell line. These findings might be useful in the elucidation of potential mechanisms involved in the clinical situation.

Antineoplastic Agents, Hormonal↗

The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy.

The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate (MPA) during postmenopausal hormone replacement therapy (HRT) in women with and without a history of premenstrual syndrome (PMS). The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden. The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle. The main outcome measures were mood and physical symptoms noted on a daily rating scale. We found that physical symptoms did not differ between 10 and 20 mg MPA. Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA. In women with previous PMS the higher dose of MPA enhanced positive mood symptoms. With respect to mood and physical symptoms, the aim to lower MPA doses in HRT is unwarranted.

Affect↗

Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small cell lung cancer.

The purpose of the study was to evaluate the effectiveness in terms of response rates, toxicity and survival of the combination chemotherapy regimen cisplatin and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was 0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N-acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks. Patients with a complete response (CR), partial response (PR) or stable disease (SD) continued the treatment, according to response re-evaluation, until 15 weeks. The present study reports the results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed (ORR 30.0%). The median follow-up period was 13 months. The median duration of response was 9 months. The median overall survival (OS) was 15 months. The one-year survival rate was 55.8%. The median progression-free survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic: neutropenia was the most significant symptom. The non-hematologic toxicity was quite low. Therefore, the treatment's toxicity was quite acceptable. There was no toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study are comparable with those observed with cisplatin plus epirubicin (ORR 39-54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly hematologic. Serum levels of proinflammatory cytokines significantly decreased after treatment.

Adult↗

A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability.

OBJECTIVE: To compare the effects of continuous combined conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA) with those of tibolone on symptom control, bleeding pattern, lipid profile and tolerability in postmenopausal women. METHODS: This was a randomized, open-label, parallel-group, multicenter study. Generally healthy postmenopausal women with an intact uterus and no contraindications to hormone replacement therapy (HRT) or tibolone were enrolled. Each subject was randomly assigned to receive CEE/MPA 0.625 mg-5.0 mg or tibolone 2.5 mg daily for 13 treatment cycles, each of 28 days. RESULTS: A total of 85 subjects were enrolled and received at least one dose of study medication, of which 76 (89.4%) subjects completed the study (n = 40, CEE/MPA; n = 36, tibolone). The incidence of postmenopausal symptoms decreased significantly over time in both treatment groups, compared with baseline, including significant decreases in the incidence of urogenital and sexual health symptoms. Significant differences in symptom control (other than hot flushes) were observed between treatment groups in a few different cycles for different symptoms, but no consistent or clinically significant trends were observed. No statistically significant differences in the incidence of bleeding were observed between treatment groups after cycle 4. Significant decreases in total cholesterol (5.6%) and low-density lipoprotein (LDL) cholesterol (7.5%) were observed at cycle 13, compared with baseline, in the CEE/MPA group, and significant decreases in high-density lipoprotein (HDL) cholesterol (8.5%) and triglycerides (13.7%) were observed at cycle 13, compared with baseline, in the tibolone group. Significant weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared with the CEE/MPA group (0.96 kg). The incidences of adverse events were similar in both treatment groups. CONCLUSIONS: Women treated with CEE/MPA or tibolone showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms, and had similar bleeding patterns after four cycles of therapy. CEE/MPA and tibolone each induced a different mix of changes in the lipid profile.

Aged↗

Phase II study of subcutaneously administered interleukin-2 in combination with medroxyprogesterone acetate and antioxidant agents as maintenance treatment in advanced cancer responders to previous chemotherapy.

An open, non-randomized phase II study was carried out including patients with advanced solid tumors who achieved an objective response or disease stabilization as a result of previous chemotherapy, to receive a maintenance treatment with recombinant interleukin-2 (rIL-2) plus medroxyprogesterone acetate (MPA) plus antioxidant agents alpha-lipoic acid (ALA) and N-acetyl cysteine (NAC). The first study endpoints were to define clinical outcome and toxicity as well as the evaluation of quality of life. As secondary endpoints we measured the changes of lymphocyte absolute count, the serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin after treatment. rIL-2 was administered at a dose of 1.8 MIU subcutaneously 3 times/week on alternate days for the first two weeks of every month and MPA was given orally at a dose of 500 mg/day at alternate days without interruption. ALA 300 mg/day orally and NAC 1800 mg/day orally were also administered continuously. Twenty-eight patients were enrolled in the study. The median duration of maintenance treatment was 10 months (6-30+). The response to maintenance treatment at September 15, 2001 was: CR 11 patients (39.3%); SD 2 patients (7.1%); PD 15 patients (53.6%). The median duration of response was 11 months (6-34+). The median follow-up duration was 11 months (6-34+). The median OS was not reached. The median PFS was 21.5 months (1-40+). The 1-year survival rate was 72.2%. At September 15, 2001, 16 patients were still surviving. No grade 3/4 toxicity and one grade 2 skin toxicity were observed. We found a significant increase of the absolute lymphocyte count and serum levels of IL-2 and a significant decrease of TNF alpha after treatment. The evaluation of patient subgroups showed the following: the patients alive at the end of study had a significant increase of lymphocyte count, IL-2 and leptin, and a significant decrease of IL-1 beta, IL-6 and TNF alpha, whereas the patients who had died had only a significant increase of lymphocyte count and IL-2. Among the patients alive, those in objective clinical response (CR + PR) + those in SD had a significant increase of lymphocyte count, IL-2 and leptin and a significant decrease of IL-1 beta, IL-6 and TNFalpha, whereas those with PD had no significant changes in any of the above values. We conclude that the combination of s.c. rIL-2 with oral MPA and anti-oxidant agents ALA and NAC in an intermittent schedule, repeated for a long-term period, is feasible, has a very low toxicity and results in the improvement of biological markers which are predictive for patient outcome.

Acetylcysteine↗

[Comparative study on two different dosages of conjugated equine estrogen continuously combined with medroxyprogesterone in prevention of postmenopausal osteoporosis].

OBJECTIVE: To investigate the effects of two dosages of conjugated equine estrogen (CEE) in preventing bone loss in early postmenopausal women. METHODS: Two hundreds and thirty six early postmenopausal women were randomly given one of the following regimens for two years. Groups A (GA): CEE 0.625 mg + medroxyprogesterone (MPA domestic made) 2 mg + caltrate-D (Ca-D) 1 tablet daily; Group B (GB): CEE 0.3 mg + MPA 2 mg + Ca-D 1 tablet daily; Group C (GC): Ca-D 1 tablet daily alone. The observation endpoints included: (1) bone mineral density (BMD) of lumbar 2 - 4 (L(2 - 4)) measured by duel energy X-ray absorptiometry (DEXA, Lunar DPX-L) before and 1, 2 years after treatment; (2) vaginal bleeding recorded daily and endometrium thickness yearly by transvaginal ultrasonography. Endometrium biopsies were performed if its thickness greater than 5 mm. RESULTS: Two hundreds and thirteen (90%) cases completed 1-year study, 176 (75%) 2 year study. In GA L(2 - 4) BMD significantly increased both after 1 and 2 year treatment as compared with pretreatment value (P < 0.001). While in GB, L(2 - 4) BMD significantly elevated only after 1 year treatment, but did not reach significance during the end of 2 year therapy. In contrast, L(2 - 4) BMD decreased by 0.4% and 1.6% respectively after 1, 2 year of GC although without significance. Compared among the three group, the increments of mean L(2 - 4) BMD after 1 year treatment in GA and GB were significantly different from, that in GC (+2.3%, +2.7% versus -0.4%, P < 0.001, P < 0.05 respectively). So were the values after 2 year treatment (+3.7%, +0.7% versus -1.6%, P < 0.001, P < 0.05 respectively). As compared the mean L(2 - 4) BMD between GA and GB, the difference reached significance only after 2 year (P < 0.01), but not after 1 year treatment (P > 0.05). The vaginal bleeding rate in GA during the first month and 1, 2 year after treatment were higher than those in GB and GC (52% versus 16%, 9%; 43% versus 12%, 2.8%; 34% versus 8%, 3.3%). Endometrium biopsies were carried in 153 cases (27 had endometrium thicker than 5 mm) in GA and GB. No atypical hyperplasia was found, but 2 cases showed simple hyperplasia in the GA. One case in GA developed superficial thromphlebitis during the 1 year treatment. CONCLUSION: Both 0.625 mg and 0.3 mg daily of CEE continuously combined with domestic MPA are effective in preventing postmenopausal osteoporosis. The former has more stronger effect than the latter, but needs higher dose of MPA when combined continuously in order to decrease the vaginal bleeding rate and preventing endometrium hyperplasia.

Alkaline Phosphatase↗

Simultaneous determination of estradiol and medroxyprogesterone acetate in pharmaceutical formulations by second-derivative spectrophotometry.

This paper reports a simple and fast method for the simultaneous determination of estradiol (ED) and medroxyprogesterone acetate (MP) in pharmaceutical formulations by second-derivative spectrophotometry. Methanol was used to extract the drugs from formulations, and subsequently the extracts were evaluated directly by derivative spectrophotometry. The drugs were determined simultaneously by using the graphic method at 297.4 nm for ED and the zero-crossing method at 273.4 nm for MP. If both compounds are present together in a sample, it is possible to quantitate one in the presence of the other. The best signal-to-noise ratio was found when the second derivative of the spectrum was used. The linear ranges for determination of the drugs were 4.7 x 10(-6) to 1.6 x 10(-4) and 7.2 x 10(-6) to 2.0 x 10(-4) mol/L for ED and MP, respectively. The ingredients commonly found in commercial pharmaceutical formulations do not interfere with the determination. Chemical and spectral variables were optimized for the determination of both analytes. Good levels of repeatability (relative standard deviation), 1.4 and 1.9%, were obtained for ED and MP, respectively. The proposed method was applied to the determination of these drugs in pharmaceutical formulations.

Chemistry Techniques, Analytical↗

[The weakest link: medroxyprogesterone acetate in pig feed].

Medroxyprogesterone acetate (MPA)-contaminated feed arrested the onset of farrowing, and induced post-lactational anoestrus in sows. Sixty percent of the sows developed cystic ovaries after weaning following exposure to pharmaceutical waste of MPA in glucose syrup. This waste ended up in acidified feed of by-products of a sow farm, and proved to be the cause of the disorders. Analysis by thin layer chromatography and Gas Chromatography/Mass Spectrometry of renal fat from 10 slaughter sows demonstrated residues of 2.5-8 ppb of MPA. Within the European Union use of MPA is illegal as growth promoter in production animals, and therefore MPA-exposed farms were placed under official control by the general inspection service. Clinical signs and diagnostic procedures of the initial case are presented and the role of the veterinary practitioner in detecting potential food safety hazards is discussed.

Anestrus↗

Plasma lipid changes and medroxyprogesterone acetate.

Progestogens may have profound effects on lipid metabolism. Effects are generally dose-related and are more pronounced with 19-nor testosterone derivatives. Progestogens suppress circulating levels of high-density lipoprotein cholesterol (HDL-C) and increase circulating low-density lipoprotein cholesterol. Therefore, over a long period of time, the risk of atherosclerosis may increase. Although contraceptive use of depot medroxyprogesterone acetate (DMPA) reduced HDL-C levels by 15-20%, the levels generally remain within the normal range. Progestogens such as DMPA usually do not have any influence on fasting triglyceride levels. Some progestogens produce changes in the composition of phospholipids, but not DMPA. Progestogen effects on lipid metabolism are different from estrogen effects alone or estrogen-progestogen combinations. Increased risk of cardiovascular disease in longterm DMPA users is probably very small, but may become more significant when coupled with high risk factors. 10 years ago, most of the undesirable metabolic changes associated with the use of oral contraceptives were attributed to the estrogen component. 2 recent findings illustrate that certain progestogens can create metabolic havoc. 1) There is a strong association between depressed circulating levels of HDL-C and risk of serious cardiovascular disesase. 2) Certain progestogens are capable of substantially depressing the circulating levels of HDL-C, whereas estrogen actually elevates HDL-C. This does not prove that progestogens cause cardiovascular disease, but this possibility should be considered.

Biology↗

Management of endometriosis with oral medroxyprogesterone acetate.

Efficacy of oral medroxyprogesterone acetate (MPA) was assessed in 35 women with an established diagnosis of endometriosis (33 pelvic and 2 abdominal). MPA was given in a dosage of 30 mg daily for 90 days. Results indicated improvement or remission in all cases, even though breakthrough bleeding occurred in 8. Twenty-six were treated for associated infertility. Twelve of these became pregnant following treatment. Pregnancy rate in those women whose husbands were fertile was 90%. Side effects included spotting and breakthrough bleeding. The patients usually remained amenorrheic and anovulatory while receiving MPA. Posttreatment resumption of ovulation was prompt. The findings indicate that oral MPA is a useful therapeutic agent in the management of minimal to moderate endometriosis, particularly when it is associated with infertility.

Abdominal Neoplasms↗

Interleukin-2, interferon-alpha and medroxyprogesterone acetate in metastatic renal cell carcinoma.

BACKGROUND: Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the main immuno-biological agents used in the therapy of metastatic renal cell carcinoma (RCC). Unfortunately the promising results obtained in biological studies have not yet been confirmed in clinical studies. One reason is linked to the immunosuppression of metastatic patients which is caused by macrophage products. IL-6 in particular is considered a growth factor for RCC. Medroxyprogesterone acetate (MPA) may interfere with IL-6 macrophage production, possibly causing a synergistic effect in association with IL-2 and IFN-alpha. Therefore the purpose of our study was to evaluate the toxicity and the efficacy of the association between IL-2, IFN-alpha and MPA. PATIENTS AND METHODS: Forty-two consecutive patients with metastatic RCC were enrolled. IL-2 was administered subcutaneously at doses of 4.5 million UI on days 1-5, 8-12, 15-19 and 22-26; IFN-alpha was administered s.c. at a dose of 3 million t.t.w; MPA was administered orally at a dose of 1000 mg daily. This schedule was repeated after a rest of 2 weeks. RESULTS: Toxicity was mild: the main symptoms observed were fatigue and fever. Six CR (14%), five PR (12%), thirteen SD (31%) and seventeen PD (41%) were observed for an overall response rate of 26%. Patients with good PS and low levels of CRP had a better prognosis. CONCLUSION: Considering both the good activity and the low toxicity of this scheme, we think that it could be carried out in normal clinical practice.

Adult↗

[Prevention of bone loss by estradiol valerate combined with medroxyprogesterone acetate among postmenopausal women with osteopenia].

OBJECTIVE: To observe the efficacy of estradiol valerate (E(2)V) combined with medroxyprogesterone acetate (MPA) in prevention of bone loss among postmenopausal women with osteopenia. METHODS: Ninety-two women 1 to 8 years after menopause with osteopenia were randomly divided into 4 groups: 1) control group: 23 cases, taking calcium carbonate (Ca) 400 mg/d+ vitamin D 200 IU/D; 2) treatment group 1: 24 cases, taking E(2)V 1.0 mg/d+ MPA 2 mg/d+ Ca 400 mg/d; 3) treatment group 2: taking E(2)V 1.0 mg/d+ MPA 2 mg/d+ Ca 400 mg/d+ vitamin D 200 IU/d; and 4) treatment group 3: taking E(2)V 1.5 mg/d+ MPA 2 mg/d+ Ca 400 mg/d+ vitamin D 200 IU/d. The bone mineral density (BMD) of L(2- 4) and neck of femur was measured by DEXA method, and the bone metabolic markers such as serum alkaline phosphatase (ALP) and urine Ca/Cr and Ntx/Cr were examined just before the drug administration and 6, 12, and 18 months after the beginning of experiment. Vaginal bleeding and breast tenderness were recorded by the subjects themselves and examined by investigators. RESULTS: Seventy-eight subjects (84.5%) were followed up for I year and 77 of them (83.7%) were followed up for 1.5 years. The fasting morning Ca/Cr remained almost unchanged in the control group, and decreased by 43.8%, 33.3%, and 33.3% by the third month respectively and then remained unchanged in the treatment groups 1, 2, and 3. The urine Ntx/Cr decreased mildly but insignificantly in the control group (P > 0.05), and decreased since the 3rd month by 42.2%, 53.2%, and 29.1% respectively in the treatment groups 1 approximately 3 and then decreased very slowly. The ALP remained almost unchanged in the control group, and decreased by 6.8%, 17.0%, and 16.4% by the 6th months respectively and by 14.2%, 17.9%, and 28.8% by the 12th month and then remained almost unchanged in the treatment groups 1 approximately 3. The BMD of L2-4 increased by 7.1% +/- 4.6%, 6.8% +/- 5.3%, and 9.0% +/- 4.0% in the treatment 1 approximately 3 by the 18th month. The BMD of neck of femur increased by 4.1% +/- 3.2%, 4.0% +/- 5.9%, and 5.9% +/- 4.8% in the treatment 1 approximately 3 by the 18th month. Fracture occurred in 2 cases of the control group and 2 cases of the treatment group because of accidents. The vaginal bleeding rate was the highest in the treatment group 3 (47.4%). The breast tenderness rates were 27.3% approximately 47.6% in the 3 treatment groups. CONCLUSION: Administration of E(2)V I mg/d combined with MPA 2 mg/d is an optional regimen for postmenopausal women with intact uterine.

Adult↗

Relationship between progesterone receptor level in endometrium and bleeding pattern in depot medroxyprogesterone acetate users.

Bleeding disturbance is the major reason for discontinuation among depot medroxyprogesterone acetate (DMPA) users. However, the causes of progestin-induced bleeding are not well understood. The aim of the study was to examine the correlation between the occurrence of uterine bleeding and progesterone receptor (PR) levels in the endometrium. Forty-five matched pairs of age and body mass index in DMPA users with bleeding and amenorrhea were studied. The endometrial PR levels were evaluated. The PR score was assessed semi-quantitatively. Forty-two subject pairs met the criteria. There was no difference in serum estradiol and progesterone levels between the groups. No correlation between the number of bleeding days and PR score nor between the number of bleeding days and serum estradiol and progesterone level was detected. The stromal PR score in DMPA subjects with amenorrhea was significantly higher than those with bleeding (p < 0.05). By contrast, the PR score in glandular endometrium was not significantly different between the groups (p > 0.05). In conclusion, after a second dose of DMPA, subjects with amenorrhea had a higher stromal PR score than those with uterine bleeding.

Adult↗