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PubMed1996

Serum immunoglobulin levels during contraceptive use of depot-medroxyprogesterone acetate in Indian women: a preliminary study.

This study was conducted to determine the effect of depot-medroxyprogesterone acetate (DMPA) as a contraceptive on levels of serum immunoglobulins, total protein and albumin in Indian users. The recommended dose of 150 mg of DMPA by deep intramuscular injection was given to twenty parous women. Levels of serum immunoglobulins, total protein and albumin were measured prior to, and at one and three months after the injection. The levels of total protein and albumin remained unaffected. No significant changes were observed in the levels of IgA and IgM. IgG levels were increased in the first and third month after DMPA injection, and the increase in the first month was statistically significant (p = 0.019). While the serum levels of IgA, IgM, total protein and albumin were unaffected, the raised levels of IgG were indicative of improved humoral immunity in Indian DMPA users.

Adult↗
PubMed1977

Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women. III. Medroxyprogesterone acetate.

The effect of medroxyprogesterone acetate (MPA) on basal circulating lipids, arginine-stimulated glucagon and insulin secretion, and glucose tolerance was studied in normal women. After 5 days of oral MPA treatment (10 mg/day), there was a small but significant decline in basal circulating triglycerides. No changes were observed in fasting plasma concentrations of cholesterol, free fatty acids, glucagon, insulin, or glucose; in the plasma glucagon, insulin, or glucose responses during L-arginine infusion; or in the plasma insulin or glucose responses during oral glucose tolerance tests. There was no correlation of any of these parameters with the observed decline in fasting plasma triglyceride concentrations. These results confirm previous reports of no consistent changes in lipid or glucose homeostasis in women using derivatives of 17alpha-acetoxyprogesterone derivatives for contraceptive purposes, and suggest that MPA may be a suitable alternative for those women who develop hyperlipemia or glucose intolerance when they use contraceptive agents which contain derivatives of ethinyl estradiol and nortestosterone.

Adult↗
PubMed1993

Medroxyprogesterone acetate decreases the sexual activity of male cynomolgus monkeys (Macaca fascicularis): an action on the brain?

Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant behavior of male sex offenders. In male cynomolgus monkeys, MPA reduces plasma testosterone (T) levels and sexual behavior, but the behavioral effects are clearly different from those of surgical castration. Because MPA is selectively taken up in unchanged form by the nuclei of neurons in the hypothalamus and preoptic area of male cynomolgus monkeys, and because it interferes with the uptake of T throughout the brain and pituitary gland, we have proposed that the behavioral effects of MPA may be mediated by brain mechanisms regulating sexual motivation that are relatively independent of circulating T levels. To test this hypothesis, eight castrated male cynomolgus monkeys bearing Silastic T implants SC were each observed during 60 min behavior tests with an ovariectomized, estrogen-treated female throughout three 4-week periods separated by 4-week periods without testing. After the first 4 weeks of testing, males received weekly IM injections of 40 mg MPA (six males) or vehicle (two males); the dose of MPA being equivalent on a body weight basis to those used clinically. Although plasma T was maintained in the upper range for intact males throughout the study, MPA treatment resulted in significantly decreased ejaculations and mounting attempts by weeks 5-6. These results demonstrated that the inhibitory effects of MPA on male behavior were independent of the reduction of plasma T levels, which points to a direct action on brain mechanisms controlling male sexual behavior.

Animals↗
PubMed1996

Binding specificity of medroxyprogesterone acetate and proligestone for the progesterone and glucocorticoid receptor in the dog.

The use of the synthetic progestin medroxyprogesterone acetate (MPA) for estrus prevention in the dog can result in overproduction of growth hormone, suppression of plasma glucocorticoid levels, and the induction of mammary tumors. Proligestone (PROL) was claimed to be devoid of these unwanted side effects. In the present study, the binding characteristics of MPA and PROL for the canine progesterone receptor (PR) and glucocorticoid receptor (GR) were investigated. The apparent inhibition constants for the PR and GR of MPA and PROL were compared with those of progesterone, ORG 2058, and a number of corticosteroids. MPA and PROL had high affinities for both the PR and the GR. The rank order for displacement of the binding of the PR ligand [3H]ORG 2058 from the canine uterine receptor was: MPA approximately ORG 2058 > PROL > progesterone >> cortisol, dexamethasone, and spironolactone. The rank order for displacement of the specific binding of the GR ligand [3H]dexamethasone from the canine liver receptor was: dexamethasone > cortisol > MPA > PROL > progesterone >> aldosterone approximately spironolactone. The apparent inhibition constants of PROL for both the PR and the GR were approximately 10 times higher than those of MPA. The ratios of the inhibition constants for the GR and PR appeared to be equal for PROL and MPA. It is concluded that although MPA has higher affinities for the PR and GR than PROL, both progestins have a similar in vitro binding specificity, which is less than that of progesterone. These findings are consistent with suppression of the adrenal cortex and the induction of growth hormone secretion in the mammary gland after MPA and PROL treatment in dogs.

Animals↗
PubMed1990

Combination of tamoxifen, aminoglutethimide, danazol and medroxyprogesterone acetate in advanced breast cancer.

Seventy-four post-menopausal women with metastatic breast cancer were treated with a combination hormonal regimen consisting of tamoxifen, aminoglutethimide danazol and medroxyprogesterone acetate (POND). 72% of the patients had received no previous treatment. The overall response rate (complete and partial remission) was 43.5% with a median response duration of 19 months and a median survival of 27 months. The most common sites of response were in regional nodes and local chest wall disease. The major side-effects were those expected from the individual agents: nausea, lethargy, rash and oedema.

Aged↗
PubMed1996

Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium.

We evaluated bleeding pattern and endometrium following the administration of two of the most common types of progestogens used in hormone replacement therapy, medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients in spontaneous menopause were randomly allocated to two groups. Group 1 (n = 14) received 5 mg/day of of MPA and group 2 (n = 14) received 5 mg/day of medrogestone: both the progestogens were sequentially added for the last 12 days of a 21-day period of transdermal estradiol administration (50 micrograms per day). A 7-day treatment-free period completed the cycle. The study treatments were administered for 6 cycles. The endomtria were checked for their thickness by transvaginal ultrasound before starting treatment and at 6th treatment cycle (days 6-10 of the estrogen-only phase and during the period between days 8 and 12 of the progestogen addition). Endometrial biopsies were performed before starting treatment only in the patients with a positive progesterone challenge test and in all the patients at the end of the study during the addition of the progestogen. The bleeding pattern was closely monitored. MPA is accompanied by a thick endometrium with full secretory transformation in all cases. On the contrary, the same dose of medrogestone induced a consistent decrease of estrogen primed endometrium with only 4 cases of full secretory transformation. Four medrogestone-treated patients dropped out due to unscheduled bleeding. A low dose of medrogestone added to transdermal estradiol induced incomplete transformation of endometrium and oligo-amenorrhea more frequently than MPA, but it increased the chances of irregular bleeding. MPA fully transformed the endometrium: periods were thus heavier but regular. None of the patients in either group had endometrial hyperplasia.

Administration, Cutaneous↗
PubMed1994

Antagonism of oestrogen-induced prolactin release by medroxyprogesterone acetate.

Previous studies conducted at our clinic suggested that the administration of hormone replacement therapy (HRT) in postmenopausal women could result in the inhibition of oestrogen-induced prolactin (PRL) release. The aim of this study was to determine how the pituitary function is affected by the sequential addition of medroxyprogesterone acetate (MPA) to oestrogen replacement therapy. Twenty-one postmenopausal women receiving no other medication were treated with a standard dose (0.625 mg/day) of conjugated equine oestrogens (CEE) for a period of 24 days, plus 5 mg/day MPA added sequentially during the last 12 days of the oestrogen therapy. Blood samples were collected before treatment, during oestrogen and oestrogen-progestogen administration and after cessation of treatment. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-oestradiol (E2) and PRL levels were studied. During treatment gonadotrophin concentrations decreased significantly, while after cessation of HRT the levels of FSH and LH increased. These gonadotrophin fluctuations indicated a sharp rise in E2 levels during therapy and a significant decrease during the treatment-free period. PRL levels were found to be higher during CEE therapy, but they fell when patients received CEE in combination with MPA. These observations suggest that the role of progestogens in a variety of experimental and clinically relevant situations needs to be investigated not only as regards their direct action but also their modulation of the effect of oestrogen.

Climacteric↗
PubMed1996

The effect of medroxyprogesterone acetate and clomiphene citrate on platelet function in menopausal women.

OBJECTIVE: We sought to determine if antiestrogens such as clomiphene citrate (CC) and medroxyprogesterone acetate (MPA) affect platelet activity in postmenopausal patients before and after treatment with estrogens. METHODS: Using an incubation study, we analyzed the effects of CC and MPA on adenosine diphosphate and adrenaline-induced platelet aggregation and on the release of adenosine triphosphate in postmenopausal patients, using a platelet study, we analyzed the effect of these drugs on platelet function. RESULTS: Platelets were inhibited by MPA and CC in the incubation study but not significantly affected in the platelet study. Platelets previously incubated with estrogen were less inhibited by CC than by MPA. DISCUSSION: Thus, platelet study to determine the optimal combination therapy for menopausal patients has indicated that CC has a non-significantly less beneficial in vitro effect on platelet function than MPA.

Adenosine Diphosphate↗
PubMed1996

Effects of continuous medroxyprogesterone acetate on lipoprotein metabolism in postmenopausal women receiving estrogen.

OBJECTIVE: To investigate the effects of medroxyprogesterone acetate (MPA) on the beneficial effects of estrogen therapy on lipid metabolism in postmenopausal women. METHODS: Postmenopausal women were administered either conjugated equine estrogen (CEE) 0.625 mg daily for 3 months (Group 1) or CEE 0.625 mg in conjunction with MPA 2.5 mg (Group 2) or MPA 5.0 mg (Group 3) daily for 3 months. Plasma levels of cholesterol, triglyceride, lipoprotein lipids, apolipoproteins, sex steroid hormones and lecithin cholesterol acyltransferase activity (LCAT) were determined. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities were measured in postheparin plasma. Changes in the lipid concentrations and enzymatic activities were evaluated in each group. RESULTS: Total, low-density lipoprotein (LDL) cholesterol, apolipoprotein B concentrations and LCAT activity were all significantly reduced by treatment in the three groups. The levels of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol as well as the levels of apolipoprotein AI and AII were significantly elevated in groups 1 and 2. The mean decrease in these parameters was related to the dose of MPA. Levels of triglyceride in the HDL and HDL2 were significantly increased in group 1. The levels of triglyceride in plasma, very low density lipoprotein (VLDL), LDL, HDL3 and VLDL cholesterol and LPL activity were unaffected. H-TGL activity was significantly inhibited only in groups 1 and 2. MPA produced a dose-dependent increase in H-TGL activity. A significant negative correlation was observed between the HDL cholesterol concentration and H-TGL activity (r = 0.58 P < 0.001). CONCLUSIONS: The administration of MPA 2.5 mg and 5.0 mg did not adversely affect the changes in VLDL-LDL metabolism produced by estrogen. However, MPA has dose-dependent negative effects on HDL metabolism by increasing H-TGL activity and the 5.0 mg MPA interferes with the favorable effects on lipids of estrogen in postmenopausal women.

Cholesterol↗
PubMedDate not supplied

Determination of medroxyprogesterone acetate in serum by HPLC with peroxyoxalate chemiluminescence detection using a fluorogenic reagent, 4-(N,N-dimethylaminosulphonyl)-7-hydrazino-2,1,3-benzoxadiazole.

The high-performance liquid chromatographic determination of medroxyprogesterone acetate (MPA) with peroxyoxalate chemiluminescence (PO-CL) detection is described. The spiked serum containing MPA was extracted on Bond-Elut C18 columns and derivatized with 4-(N,N-dimethylaminosulphonyl)-7-hydrazino-2,1,3-benzoxadiazole (DBD-H). The hydrazone of MPA with DBD-H was confirmed to be a mono-DBD-derivative. The reaction mixture was separated by direct injection onto a C18 analytical column, and quantified by PO-CL detection. The linear range of the standard curve, in serum, was 15.6-96.6 ng ml-1 with a detection limit of 9 ng ml-1 using only 100 microliters of serum, while the detection limit of standard MPA derivatized with DBD-H was 8.7 fmol per injection. The relative standard deviation of the method was 7.4% at 19.3 ng and 1.7% at 77.3 ng ml-1.

Chromatography, High Pressure Liquid↗
PubMed1994

Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer. A randomised study. The Norwegian Breast Cancer Group.

In a randomised study, 218 patients with advanced breast cancer, resistant to hormone therapy, received either doxorubicin 20 mg every week (Awkly) alone or Awkly combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 210 evaluable patients, the response rates were 26% [95% confidence interval (CI) 18-34%] for Awkly and 38% (95% CI 29-47%) for Awkly + HD-MPA (P = 0.08). There was no significant difference with regard to duration of response. Median survival was 11 months in both groups. Considerable toxicity was seen from HD-MPA, particularly weight gain and fluid retention. The present study provides evidence that, in concordance with preclinical studies and a previous randomised study, interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. For further studies, other gestagens and/or a dose reduction could be investigated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer.

The usefulness of CAF [cyclophosphamide (CPA)/doxorubicin (ADR)/5-fluorouracil (5-FU)] + medroxyprogesterone acetate (MPA) therapy for advanced/recurrent breast cancer was studied in a randomised trial at 56 institutions. Patients received CAF therapy [CPA: 100 mg, orally, days 1-14; ADR: 30 mg/m2, intravenously (i.v.), days 1 and 8; 5-FU: 500 mg/m2, i.v., days 1 and 8) in arm I, or CAF + MPA therapy (CAF + MPA 1200 mg, daily) in arm II. The response rate was significantly higher (P = 0.041) in arm II (53.5%, 46/86) than arm I (36.6%, 30/82). The response rate by tumour site was significantly higher for lymph node and bone lesions in arm II. Partial response duration and overall response duration were significantly longer in arm II. Incidences of anorexia and nausea/vomiting were significantly higher in arm I but in arm II, moon face, oedema and vaginal bleeding were significantly higher. Many patients in arm II demonstrated improvement in performance status and weight loss, suggesting a beneficial effect of MPA. The chemoendocrine therapy with CAF + MPA appears to be more beneficial than CAF alone in the treatment of advanced/recurrent breast cancer.

Administration, Oral↗
PubMed1995

Assessment of five serum marker assays in patients with advanced breast cancer treated with medroxyprogesterone acetate.

This study concerns five different tumour marker assays examined in the context of 94 patients with advanced breast cancer treated in a prospectively randomised trial of different doses of medroxyprogesterone acetate (MPA). MPA was administered at doses of 500 or 1000 mg daily and clinical evaluation of patients was carried out according to UICC criteria. Carcinoembryonic antigen (CEA) was selected as a standard marker, with three assays for MUC1 mucins (epithelial mucin core antigens (EMCA), EMCA2 and BR-MA immunoradiometric assay) differing in antibody specificities for different mucin epitopes. An additional novel assay for soluble cytokeratin was also evaluated as an example of an independent marker with a different nature and biology. Sensitivity of individual assays ranged between 44 (EMCA2) and 69% (cytokeratin) and the use of two assays in combination led to sensitivities as high as 84% (cytokeratin+BR-MA). The proportion of patients found to be assessable by each assay ranged between 51 (EMCA2) and 76% (cytokeratin). Of those patients whose marker changes were assessable, those receiving the higher dose of MPA displayed significant falls in marker levels after 12 weeks of treatment. This effect was not observed in patients receiving 500 mg. The change in cytokeratin levels in patients undergoing high dose MPA therapy proved to be most marked. Using the cytokeratin assay, 91% (of 23 patients) of patients with progressive disease showed at least a 25% rise in serum marker levels. Of these, 66% showed increases before disease progression was detected clinically with a mean lead time of 14 weeks. There was very little difference between the responses of the five tumour marker assays in patients with stable or responding disease, the proportion of these patients with stable or falling tumour marker levels ranging between 58% (CEA) and 77% (EMCA). We conclude that the cytokeratin assay has an application in monitoring response to therapy and predicting tumour progression in advanced breast cancer patients with assessable tumour marker profiles, especially if used in combination with a MUC1 mucin assay.

Adult↗
PubMed1993

Effect of onapristone and medroxyprogesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells.

We studied the influence of the antiprogestin onapristone (ZK 98.299) and the progestin medroxyprogesterone acetate (MPA) on the proliferation and hormone receptor levels of the following human breast cancer cell lines: the oestrogen receptor (ER) and progesterone receptor (PR) negative cell line MDA-MB-231 and the ER- and PR-positive cell lines T47-D and SK-BR-3. MPA and onapristone both bind to the cellular PR and can inhibit the proliferation of hormone-dependent cells; PR-negative MDA-MB-231 cells are not inhibited. The growth inhibition of the ER- and PR-positive tumour cells induced by onapristone is accompanied by a significant accumulation of cells in the G0/G1 phase and a reduction of S-phase cells, while MPA does not change the distribution of the cell cycle phases. However, MPA reduces the cellular ER content by 27% and the PR content by more than 80%. Conversely, onapristone does not significantly affect ER and PR levels. The extent of growth inhibition by both drugs differs considerably: onapristone inhibits growth of both receptor positive cell lines (T47-D:39%; SK-BR-3:17%), while MPA affected growth in only SK-BR-3 (61%). These results indicate that even though the two drugs act through the PR, the inhibitory effect on the three cell lines of MPA may depend on ER concentration and its down-regulation, while the inhibitory effect of onapristone is mainly correlated to the PR concentration without significantly affecting ER levels. Since tumour cells with low ER concentration are growth suppressed by onapristone, but not by MPA, it remains to be examined whether antiprogestins should preferably be used in PR-positive tumours with a low ER concentration.

Breast Neoplasms↗
PubMed2005

Antischistosomal action of atorvastatin alone and concurrently with medroxyprogesterone acetate on Schistosoma haematobium harboured in hamster: surface ultrastructure and parasitological study.

Aiming to study the influence of long-term administration of lipid lowering agents (atorvastatin; AV), and to study the action of combined treatment with injectable contraceptive (medroxyprogesterone acetate; MPA) on tegumental ultrastrucutre and survival of Schistosoma worms, this study was established. AV (0.9 mg kg-1) was administered orally for 49 successive days to Schistosoma heamatobium-infected hamster starting from day 35 post-infection (pi). Another group of infected hamster was administrated MPA intramuscularly (0.1 ml kg-1) at days 7 and 35 pi followed by AV treatment regimen. Both treatment regimens significantly affected the surface ultrastructure of the male worms more pronouncedly than the female ones. Combined treatment was more severe in action compared to single one. The combined treatment was characterized by losing of spines and damaging of tubercles throughout the tegument, severe erosion and peeling and appearance of deep crakes in different parts of the tegument. Moreover, mild to sever destruction to the oral suckers of both female and male worms was noticed. On the other hand, both treatment regimens significantly reduced numbers of recovered S. haematobium worms and tissue egg load. Oogram pattern was affected only in case of combined treatment with high percentage of dead eggs. In conclusion, AV, if given continuously for long time, has a pronounced antischistosomal action especially when accompanied with contraceptive intake. These promising results may encourage further investigation with the intention of their possible application on treatment of schistosomiasis as a complement strategy to praziquantel chemotherapy.

Animals↗
PubMed2005

Depot medroxyprogesterone acetate: implications for weight status and bone mineral density in the adolescent female.

Depot medroxyprogesterone acetate (DMPA) is an effective and easy-to-use contraceptive method for adolescents. However, recent literature suggests that overweight teens may be at increased risk for weight gain while on this contraceptive method, and decreases in bone mineral density have been documented in adolescents on DMPA, particularly with longer duration of use. Consideration of this new literature on DMPA and its implications for clinical practice must be done in the context of the United States having the highest adolescent pregnancy rate in the industrialized world. Hence, potential DMPA risks need to be weighed against the risk of unintended pregnancy in an adolescent.

Adolescent↗
PubMed2004

Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise.

OBJECTIVE: This study was undertaken to determine whether progestational agents can prevent inflammation-induced preterm parturition and fetal demise. STUDY DESIGN: The activation of contractile and inflammatory pathways in response to localized intrauterine inflammation was investigated by using quantitative polymerase chain reaction (PCR). Serum progesterone (P4) levels and alterations in progesterone receptor-B (PR-B) were determined with radioimmunoassay and quantitative PCR, respectively. With our in vivo model of intrauterine inflammation, animals were randomly assigned to pretreatment with P4 or medroxyprogesterone acetate (MPA) before intrauterine lipopolysaccharide (LPS). Animals were observed for preterm delivery. The number of live pups 48 hours after intrauterine LPS was recorded for each treatment group. The ability of MPA to alter signal transduction pathways leading to preterm parturition were investigated by quantitative PCR and histochemical studies. RESULTS: Intrauterine inflammation is associated with decreased serum progesterone levels and decreased transcription of PR-B. Preterm delivery rates were 100% for LPS alone, 63% for LPS+P4, and 0% for LPS+MPA. No live pups remained at 48 hours in the LPS or LPS+P4 groups. Pretreatment with MPA significantly preserved fetal viability. MPA suppressed activation of contraction-associated genes and inflammatory mediators and prevented cervical ripening in response to intrauterine inflammation. CONCLUSION: MPA, with its progestational and anti-inflammatory properties, prevented inflammation-induced preterm parturition and significantly preserved fetal viability.

Animals↗
PubMed2004

Effects of medroxyprogesterone acetate (MAP) on ovarian antral follicle development, gonadotrophin secretion and response to ovulation induction with gonadotrophin-releasing hormone (GnRH) in seasonally anoestrous ewes.

When ovulation is induced with gonadotrophin-releasing hormone (GnRH) in anoestrous ewes, a proportion of animals fail to form normal (full-lifespan) corpora lutea (CL). Progesterone treatment before GnRH prevents luteal inadequacy. It remains uncertain whether a similar effect, achieved with medroxyprogesterone acetate (MAP) from intravaginal sponges, is mediated by influences on growing ovarian follicles and/or secretion of gonadotrophic hormones, before and after GnRH treatment. Two experiments were performed, on 13 and 11 anoestrous Western white-faced ewes, respectively. Seven and six ewes, respectively, received MAP-containing sponges (60 mg) for 14 days; the remaining ewes served as untreated controls. To test the effect of timing of GnRH administration after pre-treatment with MAP-releasing sponges, GnRH injections (250 ng every 2h for 24h followed by a bolus injection of 125 microg of GnRH i.v.) were given either immediately (Experiment 1) or 24h after sponge removal in the treated ewes (Experiment 2). Ovarian follicular dynamics (follicles reaching >or=5mm in size) and development of luteal structures were monitored using transrectal ultrasonography. In Experiment 1, the mean ovulation rate (0.7+/-0.3 and 1.0+/-0.4) and proportion of ovulating ewes (57 and 67%, respectively) did not vary (P>0.05) between MAP-treated and control ewes. Normal (full-lifespan) CL were detected in 29% of treated and 67% of control ewes (P>0.05). In Experiment 2, the mean ovulation rate (2.3+/-0.2 and 1.2+/-0.6; P<0.05) and percentage of ewes with normal (full-lifespan) CL (100 and 40%, respectively; P<0.10) were greater in the treated compared to control ewes. In Experiment 1, the mean peak concentration of the GnRH-induced LH surge was lower (P<0.05) in MAP-treated than in control ewes. There were no significant differences between MAP-treated and control ewes in the characteristics of follicular waves, mean daily serum FSH concentrations, and secretory parameters of LH/FSH, based on intensive blood sampling conducted 1 day before sponging and 1 day before sponge removal. It is concluded that treatment with MAP has no effect on the tonic secretion of LH/FSH or follicular wave development in anoestrous ewes. However, the GnRH-stimulated LH discharge was attenuated in the ewes that received MAP-impregnated sponges for 14 days and were treated with GnRH immediately after sponge withdrawal. Ovulatory response and CL formation were increased when GnRH was administered 24 h after sponge removal.

Anestrus↗