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PubMed2003

Bone mineral density in adolescent and young adult women on injectable or oral contraception.

PURPOSE OF REVIEW: This report critically reviews recent original research articles that pertain to bone mineral density in young adult women utilizing injectable depot medroxyprogesterone acetate or oral contraceptives. RECENT FINDINGS: Some evidence indicates that depot medroxyprogesterone acetate and ultra-low dose oral contraceptives (containing 20 microg ethinyl estradiol) may interfere with the large increases normally observed in adolescence; however, the same degree of bone loss (or lack of bone gain) associated with these drugs is not so impressive in young adult women who would typically be experiencing small changes in bone mass. Data obtained from young adult women show that low dose (30-40 microg ethinyl estradiol) oral contraceptives seem to be more protective of bone than ultra-low dose oral contraceptives. The few extant data suggest that there may be substantial increases in bone mass after discontinuation of depot medroxyprogesterone acetate; no information is available regarding the response of bone after discontinuation of oral contraceptives. As the clinical risk for fracture is usually several decades later, several exogenous factors such as diet and exercise may exert overriding influences on later bone health. Moreover, without contraception, the clinical outcome may be unwanted pregnancy and its potential impact on bone health. SUMMARY: Recent findings suggest that depot medroxyprogesterone acetate and ultra-low dose oral contraceptives may interfere with achieving optimal peak bone mass in very young women; however, there may be substantial recovery after cessation of these methods and overriding long-term influences on bone health imposed by a myriad of lifestyle factors.

Adolescent↗
PubMed1998

Assessment of anticollagenase treatments after insertion of a keratoprosthetic material in the rabbit cornea.

PURPOSE: This study was performed to evaluate the enzyme production in response to implantation of the hydrogel material used in the experimental Chirila keratoprosthesis (KPro) and to assess the effects of five topical drugs on enzyme production and activity. KPros may be extruded from the cornea as a result of tissue melting, a process that involves excessive enzyme activity. To reduce the possibility of implant loss for the hydrogel Chirila KPro, a number of antiinflammatory drugs that have been used to treat other corneal melting conditions were investigated for their effect on initial collagenase activity after the implantation of KPro material into the rabbit cornea. METHODS: Poly(2-hydroxyethyl methacrylate) sponge pieces were implanted into rabbit corneas. Prednisolone, tetracycline, medroxyprogesterone, acetylcysteine, and sodium citrate were assessed for effects on gelatinolytic activity and stromal collagenase [matrix metalloprotease-1 (MMP-1)] production in vivo and in vitro by using zymography and Western blotting techniques. RESULTS: Whereas all five anticollagenase drugs were effective in reducing gelatinolytic activity in vitro, many were ineffective in vivo. However, medroxyprogesterone caused a reduction of gelatinolytic activity in vivo. The amount of MMP-1, as measured by immunoblotting, also was reduced by medroxyprogesterone treatment when compared with untreated controls. An increase in the apparent molecular weight of MMP-1 in operated corneas appears to be the result of the association of MMP-1 with collagen fragments resulting from the surgical trauma. CONCLUSION: This study indicates that topical medroxyprogesterone may be a useful adjunctive therapy after prosthokeratoplasty.

Acetylcysteine↗
PubMedDate not supplied

Sleep in menopause: differential effects of two forms of hormone replacement therapy.

OBJECTIVES: The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women. METHODS: Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.625 mg) and medroxyprogesterone acetate (Provera 5 mg) (n = 11) or (2) estrogen (Premarin 0.625 mg) and oral micronized progesterone (Prometrium 200 mg) (n = 10). Postmenopausal women were recorded for two consecutive nights in the sleep laboratory at baseline and again after 6 months of treatment in a randomized trial. The women also had to fill out evening and morning sleep and vigilance questionnaires for 7 days before baseline recordings and for 23 days before month 6 recordings. RESULTS: Sleep efficiency was found to be significantly improved in the micronized progesterone group. It increased by 8% (p = 0.014) with no such increase observed in the medroxyprogesterone acetate group. Time spent awake after sleep onset was also significantly improved in the micronized progesterone group but not in the medroxyprogesterone acetate group. On the other hand, menopausal symptoms and subjective measures of sleep (questionnaires) improved in both groups after treatment. CONCLUSION: This study suggests that medroxyprogesterone acetate and micronized progesterone are both effective for treating menopausal symptoms but that the latter might better improve the quality of sleep in postmenopausal women taking estrogen.

Estrogen Replacement Therapy↗
PubMedDate not supplied

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.

OBJECTIVE: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). DESIGN: Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). RESULTS: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. CONCLUSIONS: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.

Antidepressive Agents, Second-Generation↗
PubMed1980

Placental production of progesterone in ovariectomized goats treated with a synthetic progestagen to maintain pregnancy.

Pregnant goats were ovariectomized or lutectomized and treated with medroxyprogesterone acetate. The circulating concentration of progesterone, which was reduced by 85% after ovariectomy or lutectomy, increased almost 3-fold between 120 and 140 days gestation, suggesting increased placental secretion. Measurement of veno-arterial differences across the uterus confirmed that an intrauterine organ was secreting progesterone at this time. Progesterone levels decreased (by 38%) in intact animals treated with medroxyprogesterone acetate alone. Concentrations of total unconjugated oestrogens were not altered by ovariectomy or lutectomy or by medroxyprogesterone acetate alone, but were related to the birth weight of the kids. Chronic treatment with medroxyprogesterone acetate reduced milk yield during lactation by up to 64%.

Animals↗
PubMed1995

Circulating oxytocin and vasopressin is influenced by ovarian steroid replacement in women.

BACKGROUND: The posterior pituitary hormones appear to be involved in the etiology of primary dysmenorrhoea, but mechanisms regulating their release, particularly the influence of ovarian steroids, are not fully understood. METHODS: The effect of 17 beta-estradiol and medroxyprogesterone alone and in combination on oxytocin and vasopressin levels was therefore studied in 10 postmenopausal women. RESULTS: Transdermal treatment with estradiol alone by means of patches in a dose of 100 micrograms/24 h for five days resulted in an elevation of the mean plasma concentration of this hormone from undetectable to 262 pmol/l and increase in mean circulating levels of vasopressin from 0.82 to 1.22 pmol/l and of oxytocin from 2.50 to 3.98 pmol/l. Oral administration of medroxyprogesterone in a dose of 10 mg per day for 5 days, which resulted in a mean plasma level of 4.3 nmol/l, suppressed vasopressin concentrations to 0.60 pmol/l. When given after five days of treatment with estradiol, medroxyprogesterone also antagonized the stimulatory effect of the estrogen on vasopressin secretion. Medroxyprogesterone alone increased the plasma oxytocin concentration to 3.26 pmol/l, but the progestogen did not significantly influence the stimulatory effect of estradiol on oxytocin secretion. CONCLUSIONS: It is concluded that posterior pituitary hormone secretion is influenced by estradiol and progestogens, and that this may be a mechanism for the involvement of ovarian hormones in the etiology of primary dysmenorrhoea.

Administration, Cutaneous↗
PubMed2004

[Effects of the hormone replacement therapy on cardiovascular system, bone mass and memory in climacteric patients].

OBJECTIVE: To evaluate the effect of the hormone replacement therapy type estradiol-medroxyprogesterone and tibolona on cardiovascular system, bone mass and memory in the climacteric patients. PATIENTS AND METHOD: From January through December 2001 at the Specialties Hospital No. 1, we included 77 consecutive climacteric patients. They were divided in 2 groups: premenopause in treatment with estradiol-medroxyprogesterone and postmenopause with tibolona. We studied cardiovascular system, the bone mass and memory. The statistical analysis was by means of t Student for difference between the groups. RESULTS: With the estradiol-medroxyprogesterone use, the blood pressure diminished significaticantly just for systolic pressure (-10.22/-6.38 mmHg). Cholesterol and triglyceride, both diminished significantly (-43.92 mg and -58.79 mg). There is not significance for the bone mass of lumbar-spine and femoral neck (+0.68% and +0.69%) as neither in the memory test (20-22). With the tibolona use, the blood pressure was not reduced significantly (-6.93/-1.94 mmHg), with single significant reduction for cholesterol (-25.83 mg and -18.15 mg), presenting bone mass significant improvement just for femoral neck (+0.13% and +0.84%) and without improving in the memory test (17-18). CONCLUSIONS: A diminution of lipids with the estradiol-medroxyprogesterone use, as well as reduction of the cholesterol and improvement of the bone mass with the tibolona use but without benefits in the memory test with both treatments.

Adult↗
PubMed2001

[A randomized case-control study on the influence of percutaneous estradiol and progestin in cyclic combined regimen on endometrium and vaginal bleeding pattern in Chinese early postmenopausal women].

OBJECTIVE: To observe the influence of percutaneous estradiol + micronized progesterone or medroxyprogesterone on endometrium and vaginal bleeding in Chinese post-menopausal women. METHODS: A 3-year open randomized clinical study was designed. The estrogen and progestin were used continuous-combined together in a cyclic regimen. The percutaneous estradiol was regarded as estrogen. The microprogesterone (MP) and medroxyprogesterone (MPA) were served as progestin. Sixty healthy women (naturally menopausal for 1 to 5 years) were recruited and divided into four groups. The regimen as follows: (1) percutaneous estradiol gel (gel) containing 1.5 mg of 17 beta-estradiol (E2)/d plus micronized progesterone (MP) 100 mg/d in group 1 (G1, E2 1.5 + MP); (2) gel, 1.5 mg E2/d plus medroxyprogesterone acetate (MPA), 2 mg/d in group 2 (G2, E2 1.5 + MPA); (3) gel, 0.75 mg E2/d plus MP, 100 mg/d in group 3 (G3, E2 0.75 + MP); and (4) gel, 0.75 mg E2/d plus MPA, 2 mg/d in group 4 (G4, E2 0.75 + MPA). All were given for 25 d/month, and 5 days free. The transvaginal sonography was performed 0, 12, 24 and 36 months. The thickness of endometrium were measured. The endometrium biopsy by Pipelle tube was conducted at 24th or 36th months. The vaginal bleeding was recorded. RESULTS: Fifty-nine patients (98.3%) finished 1 year and 56 patients (93.3%) for 2 years, 51 (85%) for 3 years. There was no significant changes of endometrium. The thickness of endometrium before treatment in four groups were 0.25 cm, 0.27 cm, 0.22 cm, 0.28 cm and after treatment 0.37 cm, 0.30 cm, 0.326 7 cm and 0.3 cm respectively. No significant differences was found in four groups (P > 0. 05). Fifty -three patients had the Pipelle biopsy. The pathological result showed: 16 cases (25.8%) proliferated, 1 case (1.6%) secretary; 11 cases (17.7%) atrophy; 23 cases (37.1%) mixed cell; tendency to hyperplasia in 2 cases (3.2%). During the treatment, the vaginal irregular bleeding rate was highest in G2 and lowest in G3. CONCLUSIONS: Daily estrogen containing 0.75 mg and 1.5 mg E2 combined with 100 mg progesterone and 2 mg medroxyprogesterone do not increase the thickness of endometrium significantly. The vaginal bleeding rate was low when combined with 100 mg micronized progesterone. Addition of natural progesterone will low down the bleeding rate and improve the HRT compliance.

Adult↗
PubMed2006

[In vitro metabolic interaction between diphenytriazol and steroid hormone drugs].

AIM: To observe the metabolic interaction between diphenytriazol and steroid hormone drugs, and provide some useful information for clinical medication. METHODS: The steroid hormone drugs which may be co-administrated with diphenytriazol were selected, such as mifepriston, estradiol, medroxyprogesterone acetate, progesterone, norethisterone and so on. Diphenytriazol was incubated with each drug in rat liver microsome. The residual concentration of diphenytriazol or steroid hormone drugs in the microsomal incubates was determined by reversed-phase high-performance liquid chromatography, separately. The inhibition constants (K(i)) for each of them were calculated. RESULTS: The inhibition constant K(is) of diphenytriazol for the metabolism of mifepristone, estradiol, medroxyprogesterone acetate, progesterone and norethisterone were (201.3 +/- 1.0), (94 +/- 4), (128.7 +/- 2.2), (64 +/- 5) and (80 +/- 4) micromol x L(-1), respectively. The inhibition constants K(i) of steroid hormone drugs for the metabolism of diphenytriazol was (66.9 +/- 2.2) micromol x L(-1) for estradiol, (60.0 +/- 2.3) micromol x L(-1) for medroxyprogesterone acetate, (163 +/- 10) micromol x L(-1) for progesterone and (88 +/- 5) micromol x L(-1) for norethisterone, respectively. CONCLUSION: Diphenytriazol shows metabolism interaction with steroid hormone drugs such as estradiol, medroxyprogesterone acetate, progesterone and norethisterone.

Abortifacient Agents, Nonsteroidal↗
PubMed1987

Efficacy of a continuous estrogen-progestin regimen in the menopausal patient.

The major concern with the use of unopposed estrogen is its neoplastic effect on the endometrium. Progestins used to oppose the estrogen may be associated with vaginal bleeding and reversal of estrogen's protective changes in serum lipoprotein concentrations. A study was performed in which all postmenopausal women received conjugated equine estrogen for days 1-28; with group I receiving 2.5 mg medroxyprogesterone acetate for days 1-28, group II receiving 5 mg medroxyprogesterone acetate for days 1-28, and group III receiving 5 mg medroxyprogesterone acetate for days 17-28. Pre- and postdrug evaluations of the endometrium revealed atrophic changes after therapy with continuous combined estrogen-progestin. Pre- and poststudy evaluation of serum lipoprotein concentrations demonstrated significant declines in cholesterol and low-density lipoprotein cholesterol within groups I and III, and no change in group II. All patients kept a weekly diary recording any vaginal bleeding or change in vasomotor symptoms. The results suggest that a continuous regimen of 0.625 mg conjugated equine estrogen with 2.5 mg medroxyprogesterone acetate is beneficial as a primary hormonal replacement therapy for the postmenopausal patient.

Aged↗
PubMed1994

Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement.

OBJECTIVE: To study progestin administration at less than monthly intervals in postmenopausal women given continuous estrogen replacement. METHODS: Eighty postmenopausal women received 0.625 mg/day of conjugated equine estrogens for 48 weeks. Using a double-masked design, the subjects were randomized to medroxyprogesterone acetate 10 mg/day for 14 days every 28 or 84 days, or the same dosage for 28 of 84 days. Bleeding patterns, endometrial histology, and serum lipids were assessed. RESULTS: The total days of bleeding during the 48-week study were significantly reduced (P < .05) in the women given the progestin for 14 days every 3 months (mean +/- standard deviation 29 +/- 16 days) than with the other two regimens. In all groups, secretory endometrium was reported in 17-39%. At 24 but not 48 weeks, simple hyperplasia was observed in one subject in each of the less than monthly progestin groups. Significant increases (P < .05) of high-density lipoprotein cholesterol were observed before but not after medroxyprogesterone acetate in the women receiving it less than monthly. No change was seen with monthly progestin. CONCLUSIONS: In this direct comparison, medroxyprogesterone acetate given for 14 days every 3 months elicited less vaginal bleeding than standard monthly administration. Only a single woman had simple hyperplasia with each regimen of progestin given every 84 days. Medroxyprogesterone acetate given for 14 days every 3 months represents a possible alternative to standard monthly therapy if coupled with regular assessment of the endometrium.

Adult↗
PubMed2000

Interventions for treating chronic pelvic pain in women.

BACKGROUND: Chronic pelvic pain is common in women in the reproductive age group and it causes disability and distress and results in significant costs to health services. The pathogenesis of chronic pelvic pain is poorly understood. Often, investigation by laparoscopy reveals no obvious cause for pain. There are several possible explanations for chronic pelvic pain including undetected irritable bowel syndrome, the vascular hypothesis where pain is thought to arise from dilated pelvic veins in which blood flow is markedly reduced and altered spinal cord and brain processing of stimuli in women with chronic pelvic pain. As the pathophysiology of chronic pelvic pain is not well understood, its treatment is often unsatisfactory and limited to symptom relief. Currently, the main approaches to treatment include counselling or psychotherapy, attempting to provide reassurance using laparoscopy to exclude serious pathology, progestogen therapy such as medroxyprogesterone acetate, and surgery to interrupt nerve pathways. OBJECTIVES: We aimed to identify and review treatments for chronic pelvic pain in women in the reproductive years. The review included studies of patients with a diagnosis of pelvic congestion syndrome but excluded those with pain known to be caused by i) endometriosis, ii) primary dysmenorrhoea (period pain), iii) pain due to chronic pelvic inflammatory disease, or iv) irritable bowel syndrome. SEARCH STRATEGY: The search strategy adopted by the Cochrane Menstrual Disorders and Subfertility Group was used. SELECTION CRITERIA: Randomised controlled trials (RCTs) with women who had chronic pelvic pain, excluding endometriosis, primary dysmenorrhoea, pain due to chronic pelvic inflammatory disease, or irritable bowel syndrome. The reviewers were prepared to consider studies of any intervention including lifestyle, physical, medical, surgical and psychological treatments. Outcome measures were pain rating scales, quality of life measures, economic analyses and adverse events. DATA COLLECTION AND ANALYSIS: For each included trial, information was collected regarding the method of randomisation, allocation concealment, blinding, whether an intention to treat analysis could possibly be performed and relevant interventions and outcomes (see previous sections). Data were extracted independently by the two reviewers, using forms designed according to the Cochrane guidelines. MAIN RESULTS: Seven studies were identified of which four were of good methodological quality. One study was reported in a brief abstract only and was excluded. Progestagen (Medroxyprogesterone acetate) was associated with a reduction of pain during treatment. Counselling supported by ultrasound scanning was associated with reduced pain and improvement in mood. A multidisciplinary approach was beneficial for some outcome measures. Adhesiolysis was not associated with an improved outcome apart from where adhesions were severe. REVIEWER'S CONCLUSIONS: Further studies to confirm these observations are needed, together with full reporting of those studies which have been undertaken. Given the prevalence and health care costs associated with chronic pelvic pain in women, randomised controlled trials of other medical, surgical and psychological interventions are urgently required.

Chronic Disease↗
PubMed1984

Changes in the activities of microsomal enzymes involved in hepatic steroid metabolism in the rat after administration of androgenic, estrogenic, progestational, anabolic and catatoxic steroids.

Several steroids (5 beta-dihydrotestosterone, 19-nortestosterone, methyltrienolone, norethisterone, medroxyprogesterone acetate, cyproterone acetate, chlormadinone acetate and 16 alpha-cyanopregnenolone) were tested for their ability to influence the activities of three sexually differentiated hepatic microsomal enzymes (3 alpha- and 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase) in male and female gonadectomized and intact female rats. Of the steroids tested only 5 beta-dihydrotestosterone was completely ineffective. The other tested steroids elicited varying degrees of "masculinization" with a distinct gradation of effect according to the enzyme activity measured and animal model used. 5 alpha-Reductase was the most sensitive enzyme activity and 3 alpha-hydroxysteroid dehydrogenase the least. Male castrates responded better than female castrates, and these in turn better than intact females. The mechanism of action of three of the steroids (methyltrienolone, medroxyprogesterone acetate and norethisterone) was examined. Both flutamide and estradiol were able to block the action of methyltrienolone and medroxyprogesterone acetate, but not that of norethisterone. It is concluded that methyltrienolone and medroxyprogesterone acetate probably masculinize the enzyme activities by the same mechanisms as androgens, whereas the repression of 5 alpha-reductase activity elicited by norethisterone administration involves a different route.

Aminopyrine N-Demethylase↗
PubMed2003

Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium.

OBJECTIVE: To determine whether use of steroid hormone contraceptives modifies immune defense parameters of the vaginal epithelium in humans. METHODS: Vaginal biopsies were collected during the follicular and luteal phases in regularly menstruating women (controls) and in women using combined oral contraceptives, depot-medroxyprogesterone acetate injections, or levonorgestrel implants. Fifteen healthy women (aged 20-34 years) were enrolled in each group. Biopsies were analyzed in a blinded manner. Epithelial thickness was estimated by morphometry. Immune cells were analyzed by immunomorphometry with cell-type-specific monoclonal antibodies. RESULTS: The epithelium of controls harbored 241+/-35 leukocytes (CD45+ cells) per mm2 (mean+/-1 standard error of the mean), and the thickness was 261+/-16 microm. T lymphocytes (CD3+) dominated, and cytotoxic or suppressor T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7+/- 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes, and granulocytes were generally absent. There were no significant differences between the follicular and luteal phases. The epithelium was significantly thicker in all three groups that used hormonal contraceptive (333+/-9 microm) compared with controls, and it exhibited superficial hyperplasia. The frequency of intraepithelial leukocytes (CD45+) was increased in depot-medroxyprogesterone acetate (P<.001) and levonorgestrel implant users (P<.04). In depot-medroxyprogesterone acetate users, this was explained by an increased frequency of the CD8+ T lymphocyte subset. CONCLUSION: Hormonal contraceptives induce hyperplasia of the vaginal epithelium. The significant changes in the intraepithelial leukocyte population in depot-medroxyprogesterone acetate and levonorgestrel implant users most probably reflect altered local immune capacity.

Adult↗
PubMed2003

A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone.

OBJECTIVE: The purpose of this study was to determine the incidence of endometrial hyperplasia in subjects who receive continuous norethindrone acetate and ethinyl estradiol combinations versus unopposed ethinyl estradiol. STUDY DESIGN: Nine hundred forty-five postmenopausal women were randomly selected for 12 months of treatment with one of six blinded norethindrone acetate/ethinyl estradiol combinations (milligrams of norethindrone acetate/micrograms of ethinyl estradiol: 0/5, 0.25/5, 1/5, 0/10, 0.5/10, or 1/10) or to open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate. Endometrial hyperplasia and endometrial proliferation were assessed by biopsy at screening, months 6 and 12. RESULTS: Endometrial hyperplasia developed in 26 subjects: Placebo, 0/5 and 0.25/5 (1 subject each) and 0/10 (23 subjects). Significantly less endometrial proliferation was measured in the 1/5 norethindrone acetate/ethinyl estradiol and other norethindrone acetate/ethinyl estradiol combination groups and in the 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate group, than in unopposed ethinyl estradiol groups (6 months: P <.004; 12 months: P <.001). Treatment with 1/5 norethindrone acetate/ethinyl estradiol and with other norethindrone acetate/ethinyl estradiol combinations significantly reduced endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (6 and 12 months: P <.02). CONCLUSION: Norethindrone acetate protects the endometrium from estrogen-induced hyperplasia and changes in proliferative status. In addition, norethindrone acetate/ethinyl estradiol-treated subjects had significantly less endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate-treated subjects.

Double-Blind Method↗
PubMed1992

Effect of sequential and daily continuous hormone replacement therapy on indexes of mineral metabolism.

BACKGROUND: Continuous regimens of estrogen-progesterone have recently been favored over sequential regimens because of a lower incidence of withdrawal bleeding. To determine whether the beneficial effects of sequential hormonal therapy on bone metabolism are preserved with the newer continuous regimens, we studied indexes of skeletal metabolism and changes in bone mineral density during a 1-year prospective trial. METHODS: Our subjects were randomized to one of three treatment groups: those in group C-2.5 were treated with 0.625 mg of conjugated estrogen with 2.5 mg of micronized medroxyprogesterone acetate daily continuously; group C-5 received 0.625 mg of conjugated estrogen and 5.0 mg of micronized medroxyprogesterone acetate daily continuously; and group S-5 received 0.625 mg of conjugated estrogen on days 1 through 25 and 5 mg of micronized medroxyprogesterone acetate on days 14 through 25. RESULTS: At 1 year, all groups demonstrated a significant decrease in indexes of bone formation turnover, including decrements in alkaline phosphatase levels of 11% to 30% and in osteocalcin levels of 45% to 60%. Intact parathyroid hormone levels rose 10% to 20%, with a concomitant near-significant decrement in ionized calcium levels at 12 months. In addition, there were significant decrements in the 24-hour urinary calcium-creatinine ratios and hydroxyproline-creatinine ratios of 13% to 28%, measures of bone resorption. Linear regression analyses showed that the subjects with the high bone resorption achieved the greatest increment in bone mineral density in response to hormone therapy. CONCLUSION: The daily continuous estrogen-progesterone regimens are as efficacious as sequential hormonal therapy in decreasing indexes of bone turnover and stabilizing bone mineral density of the spine and proximal femur.

Bone Density↗
PubMed1983

Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes.

A number of physiological and synthetic progestins were tested for their ability to compete with [3H]dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells. As compared to the reference compound dexamethasone (relative receptor binding affinity defined as 100%), two potent synthetic progestins with a pregnane-type structure, megestrol acetate and medroxyprogesterone acetate, were found to display a considerable binding affinity towards the receptor (46 and 42%, respectively). The relative binding affinity of the naturally occurring ligand, cortisol, to the receptor was clearly lower (25%). The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid. No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [3H]Org 2058 was used. Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions. These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures. The progestin effect appears to be mediated through a radiosensitive (suppressor) subpopulation of T lymphocytes. In contrast, the synthetic progestins related structurally to 19-nortestosterone, norethisterone and d-norgestrel, were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions. These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character (e.g. suppression of the pituitary-adrenal axis) might be expected when these compounds are used in pharmacological doses.

DNA Replication↗
PubMed1987

Continuous estrogen/progestin therapy in menopause.

The incidence of vaginal bleeding, endometrial histology, menopausal symptoms, blood pressure, and serum lipid concentrations were evaluated in 26 women who received either continuous conjugated equine estrogens and medroxyprogesterone acetate (group I, N = 16) or cyclic conjugated equine estrogen + medroxyprogesterone acetate (group II, N = 10) over a 9-month treatment period. At the end of therapy, endometrial biopsy specimens in group I revealed inactive endometrium, whereas one of ten biopsy specimens in group II showed proliferative endometrium. Blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, and triglyceride levels were not significantly altered from baseline in either group during the 9-month treatment. Vaginal bleeding was virtually eliminated in group I by the end of the study, while 80% of the patients in group II continued to have cyclic menses (p less than 0.001). This pilot study suggests that continuous conjugated equine estrogen plus medroxyprogesterone acetate therapy appears to be a satisfactory method of postmenopausal hormone replacement, effectively reducing menopausal symptoms without any apparent short-term alterations in serum lipids. It has the added benefit of eliminating cyclic menstrual flow.

Biopsy↗