Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medroxyprogesterone acetate injections (Depo-Provera) were given to 625 women at 3 monthly intervals involving 693 episodes. Ages at entry to the study ranged from 15-51 years with the majority in their 20s and a mean age of 30. Length of exposure ranged from 3-168 cycles. 4 women have received more than 160 continuous cycles of DMPA. Of the medication-induced reasons for discontinuing DMPA, bleeding was the most common with an incidence of 10.5% followed by depression (1.4%), weight gain (1.4%), and loss of libido (1.6%). No patient ceased treatment because of headaches, recurrent vaginal infections, mastalgia, nausea, chloasma, hypertension, or other vascular illnesses. The 59 women who move away or were lost to follow-up accounted for 405 cycles of treatment. The solitary unplanned pregnancy occurred in a 28-year-old obese woman who had previously had other method failures, once with an IUD and once with oral contraceptives (OCs). No association was found with carcinoma of the cervix. Of 80 women ceasing treatment to become pregnant, only 1 women has required the assistance of chlomiphene and conceived 2 years after ceasing DMPA. Amenorrhea was the side effect most appreciated by the women using DMPA. Due to the problem of irregular bleeding, it is wise to warn prospective patients about the lack of bleeding control that they have 1 chance in 10 of having relative menorrhagia. Women using OC subject to frequent vaginal moniliasis had a marked reduction in episodes after switching to DMPA. Chloasma, 1 of the minor stigmas of OC, was not induced in any of the patients. DMPA is a safe and efficient reversible method of contraception for women who have various gynecological conditions or problems associated with using OCs.
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PMID:Medroxyprogesterone acetate as an injectable contraceptive. 296 70

The antiepileptic effect of progesterone, 5-alpha-pregnane-3,20-dione, 3-alpha-hydroxy-5-alpha-pregnane-20-one, and 3-alpha-hydroxy-5-beta-pregnane-20-one were tested in an experimental animal model, and compared with the effect of clonazepam. The steroids were dissolved in serum from ovariectomized cats. Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin-soaked filter papers on the ipsi and contralateral cerebral cortex. The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer. The changes in frequency and amplitudes were calculated. The drugs were infused during 20-s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min-1. A penicillin focus on the contralateral hemisphere served as a simultaneous control. Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf. Table I). The 5-alpha-pregnane-3, 20-dione was generally less potent than progesterone (median reduction 9%) and the 5-alpha- and 5-beta-pregnanolones were two to three times more potent than progesterone (54-66% reduction). The latency of the inhibitory effect was 4-10 s measured from the entrance of the infusion into the lingual artery. The depression lasted 10-20 min. It is concluded that the pregnanolones have strong antiepileptic properties. The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels.
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PMID:The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex. 367 11

Purified porcine relaxin (3000 U/mg) was administered im (RLX-IM; 1 mg; n = 2) and in the cervical os (RLX-OS; 1 mg; n = 2) on day 273 (approximately 10 days before parturition normally occurs) of gestation to determine the profiles of immunoreactive relaxin and its effects on progesterone, estrone (E1), and 17 beta-estradiol (17 beta-E2) secretion in peripheral blood plasma of beef heifers. Controls received either 0.01 M PBS (1 ml, im; n = 2) or 0.01 M gel-PBS (gel; 1 ml, os; n = 2) in cervical os. One relaxin-treated (im) heifer calved at 4 h and 36 min after treatment; thus, data from this heifer were not included in subsequent analysis. Relaxin-treated heifers showed an acute elevation in relaxin, a precipitous decrease in progesterone, and a significant (P less than 0.05) elevation of E1 and 17 beta-E2. Plasma relaxin levels were 4.95, 1.5, and 0.24 ng/ml at 0.5 h in RLX-IM, RLX-OS, and control animals, respectively. Peripheral plasma relaxin peaked between 23-31 ng/ml 1-2.5 h before returning to less than 0.5 ng/ml 5-12 h after treatment. Relaxin administration accounted for 70%, 73%, and 58% of the progesterone, E1, and 17 beta-E2 variability between treatments, respectively. An abrupt decrease (P less than 0.01) in progesterone preceded the rises (P less than 0.05) in E1 and 17 beta-E2 at 1.5, 2-2.5, and 2-3.5 h, respectively. Maximum progesterone deviations from the pretreatment mean concentration were -5.43, -3.05, and -0.92 ng/ml for RLX-IM, RLX-OS, and controls. Progesterone rebounded from 36% to 61% and 62% to 79% of respective pretreatment means for RLX-IM and RLX-OS. Peak elevation of E1 was 407.3, 306.5, and 71.5 pg/ml and that of 17 beta-E2 was 82.2, 35.8, and 7.8 ng/ml for RLX-IM, RLX-OS, and controls, respectively. These results provide strong evidence that a pharmacological dosage of relaxin induces an acute depression of progesterone secretion beginning within 90 min in beef heifers during late pregnancy. We suggest that these early and marked luteolytic effects of relaxin on progesterone secretion in cattle could be by direct or indirect actions via mechanisms that are yet unknown.
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PMID:Acute decrease in progesterone and increase in estrogen secretion caused by relaxin during late pregnancy in beef heifers. 378 May 65

We studied eight women who had complex partial seizures and anovulatory cycles or inadequate luteal phases. Progesterone suppositories were given during the premenstrual phase or entire second half of the cycle in doses of 50 to 400 mg q12h. Antiseizure medication levels were kept in the therapeutic range. Average monthly seizure frequency declined by 68% (p less than 0.05, Wilcoxon matched-pairs test) in a 3-month treatment period compared with the 3 months prior to therapy, and six of the eight women had fewer seizures. None experienced more seizures or disruption of menses. Transient tiredness and depression were noted in some when progesterone dosage was raised above minimally effective levels. These symptoms cleared within 48 hours of lowering the dosage. The value of intermittent natural progesterone therapy as a safe, well-tolerated, and effective adjunct to antiseizure therapy should be assessed further.
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PMID:Intermittent progesterone therapy and frequency of complex partial seizures in women with menstrual disorders. 378 77

The contractability of the Fallopian tubes is instrumental in the transport of the ovum to the uterus. Various studies have been done to determine the effect of different hormones on this property of the tubes, but they have been inconclusive. 34 patients who were scheduled for salpingectomies for reasons of birth control and who had been using steroid contraceptives for at least 3 months prior to the operation were selected for study. Half the sample had used pure progestagens (Depo-Provera or chlormadinone) and half had used a combined preparation (quinestrol + quingestanol or deladroxate). All were between 29-41 years of age with numbers of pregnancies ranging from 5 to 21. The intensity and frequency of the contractions and the general activity of the isthmus portion of the tubes were studied for 10-minute periods in 2 cm segments. Also, histological studies were done using hematoxylin eosin tincture and Van Giessen tincture, and histochemical tests were performed. The 17 cases on combined orals exhibited a significantly higher rate of activity than those on pure progestins, but were also subject to contractions of greater intensity. The histochemical studies showed a decrease in the energetic material and in the enzymatic activity related to carbohydrate metabolism in the tubes of the progestin group. The depression of motor activity and energetic metabolism was, however, neutralized by administering estrogens.
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PMID:[Effects of various steroids on the morphology and function of human fallopian tubes]. 419 46

Adrenocortical function was studied in 10 women receiving norethindrone 2 mg plus mestranol 100 mcg ("maxi" pill) and in 10 women receiving norethindrone .35 mg ("mini" pill) over a 9-month period; plasma cortisol levels (8 a.m. and 3 p.m.), 24-hour urinary cortisol levels, and cortisol secretion rates were measured on Days 10 and 24 of the menstrual cycle. Prior to therapy, during a normal menstrual cycle, 18 of 20 showed a significant peak of luteinizing hormone (LH) which was considered presumptive evidence of ovulation. The 9th cylce during therapy showed: 1) no significant difference between plasma and urinary cortisol on Days 10 and 24, 2) a significant increase in plasma cortisol concentrations at 8 a.m. and 3 p.m. on Days 10 and 24 with the maxi pill in comparison to pretreatment levels, 3) a significant decrease in plasma cortisol at 3 p.m. on Day 10 with the mini pill but no change at other times, 4)a significant decrease in cortisol secretion rate on Day 24 with the maxi pill but no change with the mini pill, and 5) a significant decrease in urinary cortisol levels with the maxi pill on Days 10 and 24 and with the mini pill on Day 10. The mini pill results suggest that progesterone may be responsible for depression of adrenocortical acitivity during the luteal phase. Rise in plasma cortisol concentration probably occurred because of a corresponding rise in corticosteroid-binding globulin concentration induced by the estrogen. Progesterone is likely responsible for halting cortisol production and/or release.
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PMID:Adrenocortical function studies during the normal menstrual cycle and in women receiving norethindrone with and without mestranol. 506 Mar 81

Postmenopausal patients with metastatic breast cancer were treated with medroxyprogesterone acetate (MPA) (Clinovir) in dosages between 500 and 1500 mg orally per day. The relation of MPA plasma concentrations and endocrine effects were studied in a longitudinal fashion. MPA exerted suppressive effects on the basal and gonadotropin-releasing hormone (GnRH) stimulated gonadotropin secretion, cortisol, dehydroepiandrosterone (DHEA), and estradiol (E2) in a dose-dependent manner leading to a complete suppression with 1500 mg orally per day. The depression of thyroid hormones (T3 and T4) coincided with a depression of the thyroxine-binding index (TBI). MPA did not affect human growth hormone (hGH), basal and thyrotropin-releasing hormone (TRH) stimulated thyroid-stimulating hormone (TSH) and aldosterone. Basal and TRH-stimulated prolactin (PRL) secretion showed a slight but distinct elevation. From these data it is concluded that in postmenopausal patients MPA exerts its antitumor activity by an interference with the hypothalamo-pituitary adrenal axis in the sense of a selective pharmacologic hypophysectomy leading to complete suppression of adrenal steroid secretion. Additionally, MPA inhibits tumor cell growth through the progesterone receptor. A dual mechanism for the antitumor activity of high dose is postulated MPA: ablative through suppression of the hypothalamo-pituitary-adrenal axis and subsequent estrogen deprivation, and additive via the progesterone receptor directly on the tumor cell. The significance of gonadotropin suppression in the postmenopause for breast cancer growth is unclear. The depression of T3 and T4 is due to a depression of thyroid hormone-binding proteins. The elevation of PRL secretion may be explained by a slight estrogenic activity of MPA metabolites.
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PMID:Pharmacokinetic and pharmacodynamic basis for the treatment of metastatic breast cancer with high-dose medroxyprogesterone acetate. 608 20

Pituitary glands of proestrous (PRO) rats display enhanced LH secretory response to LHRH when compared to pituitary glands of estrous (EST) rats. In addition proestrous pituitary glands display a self-potentiating (priming) response to LHRH, whereas estrous pituitary glands do not. This study addresses the role of the proestrous surge of progesterone in converting the proestrous-like LH secretory responses of the pituitary gland to those of estrus. Anterior pituitary glands were obtained from PRO and EST rats. In addition, Pro rats were treated with pentobarbital alone (PRO/PB) or with pentobarbital plus progesterone (PRO/PB-P4). Pentobarbital was given to prevent proestrous surges of LH and progesterone. Pentobarbital-treated animals were killed the day after treatment, estrus. Pituitary glands from each group were tested for LH secretory response in a superfusion chamber with exposure of two 15-min pulses of 10 nM LHRH separated by 90 min, or assayed for LHRH receptor content using iodinated D-Ala6-LHRH. Anterior pituitary glands from PRO rats secreted higher levels of LH than EST rats in response to an LHRH pulse. Only PRO anterior pituitary glands secreted priming responses to LHRH. Though anterior pituitary glands obtained from pentobarbital-treated rats showed LH responses of similar magnitude to anterior pituitary glands of PRO rats after initial LHRH challenge, they did not display priming responses. Progesterone replacement (PRO/PB-P4) led to depressed secretory responses when compared to PRO pituitary glands similar to EST rats. LHRH receptor concentrations in pituitary glands of EST rats was lower than those in pituitary glands of PRO rats. Depression of pituitary LHRH receptor concentration from proestrus to estrus was prevented by pentobarbital-treatment on proestrus. Estrus-like depression of receptor concentration was restored after progesterone treatment (PRO/PB-P4). These data suggest the LHRH receptor depression on estrus is a consequence of the secretion of progesterone on proestrus. Further, the declining magnitude of the in vitro LH-secretory response to LHRH follows a declining LHRH receptor concentration; however no correlation exists between receptor number and ability to prime.
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PMID:Secretion of luteinizing hormone (LH) and pituitary receptors for LH-releasing hormone as modified by the proestrous surge of progesterone. 609 51

Noradrenergic (alpha 1 and beta) and serotonergic (5HT1 and 5HT2) receptors were assayed in the brains of ovariectomized female rats treated for 2 weeks with estrogen, progesterone or a combination of both hormones. Estrogen treatment resulted in a decrease in the number of 5HT1 and beta adrenergic receptors, with a concomitant increase in 5HT2 receptors. Progesterone alone caused a smaller increase in 5HT2 receptors, a similar decrease in 5HT1 and had no significant effect on noradrenergic receptors. When given with estrogen, progesterone blocked the estrogen effect on 5HT2 receptors but did not inhibit the estrogen-mediated decrease in 5HT1 and beta adrenergic receptors. alpha 1 adrenergic receptors were not affected by any of the hormone treatment paradigms. beta adrenergic and 5HT2 receptors are often implicated in antidepressant action, and the modulation of these two receptor types by ovarian hormones might be relevant to hormone-linked affective changes such as premenstrual tension and post-partum depression.
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PMID:Serotonergic and noradrenergic receptors in the rat brain: modulation by chronic exposure to ovarian hormones. 618 18

The antitumor effect and side effects of oral high-dose Medroxyprogesterone acetate (MPA) therapy were studied in 110 patients with advanced or recurrent breast cancer. MPA in 200 mg tablets was consecutively administered at a daily dose of 600, 800, 1,000, 1,200, 1,600, 1,800 or 2,400 mg. The overall response rate was 32/110 (29.1%), and the highest response rate was obtained in the 1,200 mg group (38.2%). The response rate by the site of lesion was higher in the soft tissues and also in bone metastases. Side effects such as moon face, vaginal spotting and abnormal glucose tolerance was mild and tolerable. Accordingly, from the antitumor effect and side effects, the optimal dose was considered to be 1,200 mg a day. Furthermore, as MPA therapy increases appetite and body weight of patients without causing myelopoietic depression, this drug could be used successfully in combination with other chemotherapeutic agents.
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PMID:[Oral high-dose medroxyprogesterone acetate (MPA) in the treatment of advanced and recurrent breast cancer: a dose-response evaluation]. 622 90


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