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PubMed2001

A prospective, controlled study of the effects of hormonal contraception on bone mineral density.

OBJECTIVE: To compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18-33 years of age with those not using hormonal contraception. METHODS: Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill (n = 28) or a desogestrel-containing pill (n = 35). Fifty-nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups. RESULTS: Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills (P = .01), but not among users of desogestrel-containing pills (P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < .002). CONCLUSION: Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible.

Adolescent↗
PubMed2000

The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins.

OBJECTIVES: To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. SETTING: In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. SUBJECTS: Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. INTERVENTIONS: The women were randomized to HRT, i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. MAIN OUTCOMES: Effects on lipids and lipoproteins. RESULTS: After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. CONCLUSIONS: In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Administration, Cutaneous↗
PubMed2000

Optimizing continuous-combined hormone replacement therapy for postmenopausal women: a comparison of six different treatment regimens.

OBJECTIVE: We sought to determine the optimum estradiol valerate-medroxyprogesterone acetate regimens for efficacy and safety. STUDY DESIGN: We performed a 24-month, randomized, double-blind phase II study. Four hundred nineteen women who were postmenopausal for at least 3 years were placed in six parallel treatment groups and received 1 or 2 mg estradiol valerate with either 2.5 or 5 mg medroxyprogesterone acetate. In two groups the dose of estradiol valerate was increased from 1 to 2 mg estradiol valerate after 6 months. RESULTS: A marked improvement of climacteric symptoms was observed, and most women had no bleeding even during the first 3 months of treatment. The best bleeding pattern was achieved with 1 mg estradiol valerate and 2.5 or 5 mg medroxyprogesterone acetate, and in most groups the bleeding pattern improved over time. No cases of hyperplasia were observed. CONCLUSION: All regimens alleviated climacteric symptoms and provided excellent bleeding control, even during the early weeks of treatment. A choice of various dose combinations offers flexibility of dosing, thus enabling therapy to be tailored to the needs of individual women.

Bone Density↗
PubMed2000

Progestins abrogate estrogen-induced changes in the insulin-like growth factor axis.

OBJECTIVE: We sought to investigate the effect of oral progestins on estrogen-mediated changes in the insulin-like growth factor axis in the peripheral circulation. STUDY DESIGN: Oral conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, desogestrel, or norethindrone was given in a randomized triple-crossover fashion to 10 healthy postmenopausal women, and the effects on the insulin-like growth factor axis were determined. RESULTS: Baseline circulating insulin-like growth factor I levels were significantly reduced by conjugated equine estrogen (359 +/- 54 vs 225 +/- 44 ng/mL; P =.0001). This effect was reversed by progestins (medroxyprogesterone acetate, 254 +/- 44 ng/mL; desogestrel, 266 +/- 50 ng/mL; norethindrone, 286 +/- 48 ng/mL; F = 12.2; P =.0015). Free insulin-like growth factor I was reduced by conjugated equine estrogen (1.00 +/- 0.15 ng/mL vs 2.10 +/- 0.39 ng/mL; P =.004), but addition of progestogens had no further effect. Insulin-like growth factor II and insulin levels were unaffected by conjugated equine estrogen or progestins. Plasma insulin-like growth factor binding protein 1 concentration increased significantly from baseline with conjugated equine estrogen alone (44.1 +/- 6.0 vs 154 +/- 30 microg/L; P =.003). This rise was opposed by progestins of increasing androgenicity (medroxyprogesterone acetate, 130 +/- 26 microg/L; desogestrel, 100 +/- 16 microg/L; norethindrone, 78.0 +/- 12 microg/L; F = 12.5; P =.0015). Insulin-like growth factor binding protein 3 levels fell with conjugated equine estrogen, and this was reversed by progestins (conjugated equine estrogen, 2.17 +/- 0.13 mg/L; vs norethindrone and conjugated equine estrogen, 2.41 +/- 0.12 mg/L; F = 7.6; P =.01). Insulin-like growth factor binding protein 4 levels increased with conjugated equine estrogen with or without progestins, whereas insulin-like growth factor binding protein 2 levels were unchanged. CONCLUSIONS: Coadministration of androgenic progestins abrogates estrogen-related changes in circulating insulin-like growth factor I, insulin-like growth factor binding protein 1, and insulin-like growth factor binding protein 3. Such hormone replacement therapy-induced changes may have significant consequences for the development of cardiovascular disease and osteoporosis and implications for the use of insulin-like growth factor I in monitoring growth hormone replacement.

Cross-Over Studies↗
PubMed1994

Combined chemo-immuno-hormonotherapy of advanced renal cell carcinoma.

Thirty-five patients (pts.) with advanced renal cell carcinoma were treated with a combination of vinblastine (5 mg/m2/IV) plus epirubicin (50 mg/m2/IV) every 3-4 weeks, alpha-2-A-interferon (9 x 10(6) U/IM 3 times in the 1st week, then 18 x 10(6) U/IM 3 times weekly), and medroxyprogesterone acetate (2,000 mg/os/day plus 500 mg IM/week). Thirty-one patients were males and 4 were females with a median age of 63 years (range 35-75) and median performance status of 70% (range 50-90%). We observed nine partial remissions (26%) with median duration of 40 weeks (range 20-232+). Fifteen pts. had no change (43%) while 11 pts. progressed (31%). The main side-effects were: leukopenia (29/35, 83%) with median nadir of 3,100 WBC/mm3 (range 510-3,990) and fever (32/35, 91%). Thrombocytopenia occurred in 4 pts. (11%), anemia in 5 (14%), asthenia in 12 (34%), nausea/vomiting in 12 (34%), alopecia in 8 (23%) and stomatitis in 3 (8.5%). Two patients stopped the therapy with medroxyprogesterone acetate because of muscular cramps. Median survival was 65 weeks (range 6-327+). We conclude that the combination of recombinant alpha 2A-interferon-vinblastine-epirubicin and medroxyprogesterone acetate has modest but definitive activity in patients with advanced renal cell carcinoma.

Adult↗
PubMed2001

Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women.

BACKGROUND: Studies showed that hormonal fluctuations that occur over the human menstrual cycle affect energy intake and expenditure. However, little is known about the possible effects on body weight regulation that may arise when these cyclic changes are suppressed with hormonal contraceptives. OBJECTIVE: The aim of this study was to examine how a progestational contraceptive drug (depot medroxyprogesterone acetate) affects food intake, resting energy expenditure (REE), and body weight in young women. DESIGN: Twenty normal-weight women were tested in a single-blind, placebo-controlled experiment. Body weight, REE, and 3-d food intake (food provided) were measured in the follicular and luteal phases of 2 menstrual cycles before a single injection of depot medroxyprogesterone or saline solution was administered. Measurements were also taken 4 times after injection: in the luteal and follicular phases of 2 cycles in the placebo group and 2 wk apart (to mimic timing of the menstrual phases) in the drug group. RESULTS: Before injection, the phase of the menstrual cycle affected both energy intake and REE. The study participants consumed more energy (4.3%; P = 0.02) and expended more energy at rest (4.3%; P = 0.0002) in the luteal phase than in the follicular phase. Comparison of pre- and postinjection means showed that treatment with the contraceptive drug had no significant effects on energy intake, REE, or body weight. CONCLUSIONS: This study showed that, although phases of the menstrual cycle affected energy intake and REE, depot medroxyprogesterone acetate did not alter energy intake or expenditure or cause weight gain in young women.

Adult↗
PubMed1995

Influence of a cigarette smoke extract on the hormonal regulation of platelet-activating factor acetylhydrolase in rats.

We evaluated the effects of estrogen, progestin, and cigarette smoke extract (CSE) on plasma platelet-activating factor (PAF) acetylhydrolase (AH; PAF-AH) activity in rats. The effects on rat tissues of an i.v. injection of PAF were studied as part of our investigation of the mechanisms involved in thrombotic episodes. Plasma PAF-AH activity in adult female rats (14 wk of age) treated with 17 alpha-ethynylestradiol (100 micrograms/kg, 5 days) was decreased by 70%. Medroxyprogesterone (50 mg/kg, 5 days) increased PAF-AH activity by 50%. CSE (0.5 cigarette/kg, 5 days) did not alter PAF-AH activity during the treatment. However, a combination of CSE and 17 alpha-ethynylestradiol decreased plasma PAF-AH activity by 90%. The decrease in PAF-AH activity was age-dependent. The effect of medroxyprogesterone on plasma PAF-AH activity was not influenced by CSE. When PAF (5-40 nmol/kg) was injected i.v. into untreated adult female rats, 9 of 16 animals died after a 20-nmol/kg dose of PAF. Macroscopic findings included hemorrhage, hyperemia, and congestion in the lungs and heart, and necrosis-like changes in the gastrointestinal tract. Microscopically, thrombi were observed in the lungs and heart. When PAF was administered to adult female rats pretreated with sex steroid hormones, the mortality of rats with low plasma PAF-AH activity caused by 17 alpha-ethynylestradiol was increased but that of rats with high PAF-AH activity caused by medroxyprogesterone was decreased. Thus, PAF and PAF-AH may play important roles in the thrombotic episodes known to occur in female smokers who use oral contraceptives.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Effects of tibolone on bone quality in ovariectomized monkeys.

OBJECTIVE: The purpose of this report is to examine the effects of two doses of tibolone on bone quality (bone biomarkers, bone density, and bone strength) in ovariectomized cynomolgus monkeys fed high-fat diets. DESIGN: Ovariectomized cynomolgus monkeys were randomized into one of five treatment groups: placebo-treated control, tibolone (0.2 mg/kg/day), tibolone (0.05 mg/kg/day), conjugated equine estrogens (Premarin, 0.042 mg/kg/day), and conjugated equine estrogens plus medroxyprogesterone acetate (0.042 and 0.167 mg/kg/day, respectively). Bone quality was assessed by determining bone strength and density in vertebrae and femora collected after 24 months of treatment. RESULTS: Monkeys treated for 24 months with tibolone had increased bone mineral density in the distal femur and improved biomechanical properties in the midshaft femur compared with placebo-treated ovariectomized monkeys, as did monkeys treated with conjugated equine estrogens with or without medroxyprogesterone acetate. No treatment effects were seen in lumbar vertebra bone density or strength. There was no significant difference between tibolone and estrogen on biomechanical properties of the femur. CONCLUSION: These data show that tibolone is comparable to conjugated equine estrogens with or without medroxyprogesterone acetate in decreasing bone turnover and increasing bone strength in ovariectomized monkeys.

Alkaline Phosphatase↗
PubMed2002

8-Chloro-cAMP-related changes on mice uteri.

Histopathological effects of cAMP analog (8-Chloro-cAMP), tamoxifen, and medroxyprogesterone, alone or combined, upon BALB/c mice uteri are reported. 8-Chloro-cAMP diminished uterine weight, but did not modify its histopathology or estral cycle significantly. Tamoxifen diminished uterine weight showing cystic hyperplasia and an estral cycle arrested at diestrus. Medroxyprogesterone increased uterine weight, caused a swelling of the endometrium and a pseudopregnancy estrus. When combined with 8-Chloro-cAMP, tamoxifen or medroxyprogesterone always had a predominant effect. We concluded that the effects of 8-Chloro-cAMP on mice uteri did not cause significant changes on its histopathology, but diminished its weight.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Human dermal fibroblast cells express prolactin in vitro.

This study demonstrates the synthesis and release of prolactin (PRL) from dermal fibroblasts (>98%) in vitro, suggesting a potential local source of PRL in skin. PRL release was first detected in confluent cultures (0.25 x 10(6) plated cells) on or before day 18 and increased to a maximal level of 2 ng/72 h by day 30. Medroxyprogesterone acetate and estradiol (E2) had no effect on PRL release, but prostaglandin E2 (PGE2) reduced the time required for PRL induction to 6-9 days. The steroids and PGE2 together were synergistic, reaching maximal values of approximately 10 ng/72 h after 2 or more weeks of treatment. Dibutyryl-cyclic AMP, a second messenger in prostaglandin signal transduction, was also synergistic with medroxyprogesterone acetate and E2, but induced significant PRL expression in the absence of the steroids (28 and 12 ng/72 h, respectively). The increase in PRL release was not a result of increased cell proliferation, because the PRL-secreting cultures had 32.2 +/- 8.8% less DNA (N = 3 individuals, 93% confidence limit) than control cultures after 3 weeks of treatment with dibutyryl-cyclic AMP, medroxyprogesterone acetate, and E2. Dermal fibroblast PRL was immunologically and electrophoretically identical to decidual and pituitary PR-Ls, and Northern blot analysis demonstrated a PRL mRNA size of 1.15 kb. Maximal PRL release from fibroblast cells was 32.0 +/- 6.1 ng/72 h (mean +/- SD at 95% confidence limit) for a donor population representing both males (n = 15) and females (n = 7) between the ages of 20-week gestation to 52 years. In contrast to term decidual fibroblast cells that also express PRL, dermal fibroblasts did not co-express insulin-like growth factor-binding protein-1.

Blotting, Western↗
PubMed1970

Failure of a pure progestogen contraceptive to affect serum levels of iron, transferrin, protein-bound iodine, and transaminase.

Medroxyprogesterone acetate, a pure progestational agent which is not metabolized to oestrogen, was given to 30 women and shown to have no effect on the serum levels of iron, total iron-binding capacity, transferrin, and protein-bound iodine. Eighteen of these women had previously taken oral contraceptives of the combined oestrogen-progestogen "sequential" type, and during that time these serum levels were raised. Nevertheless, the levels all fell significantly after medroxyprogesterone acetate was given and the "sequential" oral contraceptive was stopped. In a further 12 postpartum women the serum levels did not change significantly after medroxyprogesterone acetate.These observations strongly suggest that raised plasma protein levels resulting from the administration of oral contraceptives are due to the oestrogen component.

Adolescent↗
PubMed1980

Determinants of chronic carbon dioxide retention and its correction in humans.

17 patients with chronic ventilatory failure (including 14 with chronic obstructive pulmonary disease) were studied to determine the causes of carbon dioxide retention and the chronic effect of medroxyprogesterone acetate on ventilatory drive and acid-base status. Carbon dioxide retention in patients with high mechanical loads occurred concomitantly with a higher than normal inspiratory effort (mouth occlusion pressure) and normal minute ventilation to carbon dioxide production ratio (Ve/Vco(2)); but with shortened inspiratory time (1.3+/-0.1 vs. 1.8+/-3 s), increased breathing frequency (17+/-1 vs. 14+/-1 breaths/min), low tidal volume (0.57+/-0.03 vs. 0.88+/-0.04 L), and high dead space to tidal volume ratio (0.63+/-0.02 vs. 0.39+/-0.07). Using a randomized application of treatment and placebo conditions, it was shown that 4 wk of medroxyprogesterone acetate caused significant reductions in Paco(2) (from 51+/-1 to 42+/-1 mm Hg) in 10 of 17 patients. This "correction" of Paco(2) in these patients was associated with increases in mouth occlusion pressure (14%), tidal volume (11%), and alveolar ventilation (15%) compared to placebo, although inspiratory time remained shortened. Arterial and lumbar cerebrospinal fluid pH was alkaline compared to placebo in patients who "corrected" Paco(2). No change was noted in lung mechanics or core temperature. Common prerequisites for correction of Paco(2) with medroxyprogesterone acetate treatment were the ability to significantly lower Paco(2) upon acute voluntary hyperventilation and to increase tidal volume rather than breathing frequency in response to the drug. We attribute chronic CO(2) retention in these patients to alterations in respiratory cycle timing and to a neuromuscular inspiratory effort which is adequate for the level of tissue CO(2) production, but inadequate in the presence of mechanical and ventilation-perfusion abnormalities to normalize arterial blood gases.

Acid-Base Equilibrium↗
PubMed1977

Regulation of lactogenic hormone binding in rat liver by steroid hormones.

We have measured the effects of testosterone propionate, medroxy-progesterone acetate and cortisol on the binding of ovine [125I]iodoprolactin to 100,000 X g particulate fractions from liver of normal and estrogen-treated female rats. In untreated animals 6.7 +/- 1.1% (SD) of the radioactivity added to 0.5 mg of membrane protein was specifically bound to the hormone receptor. Specific binding was significantly (P less than .05) decreased after 7 daily doses of testosterone (1.0 mg) to 2.8 +/- 1.4%, medroxyprogesterone (0.25 mg) to 2.7 +/- 0.2% and cortisol (5.0 mg) to 3.1 +/- 1.3%. The serum prolactin concentration, 4.2 +/- 3.4 ng/ml in normal animals, was not affected by the hormone treatment. Ethinyl estradiol, 10 mug/day for 7 days, increasing the binding of [125I]iodo-prolactin to 16.6 +/- 6.0% and increased serum prolactin to 50.6 +/- 11.5 ng/ml. Simultaneous administration of testosterone, medroxyprogesterone or cortisol with estradiol did not diminish the estradiol-induced increase in serum prolactin, but completely prevented the increase in prolactin binding. Testosterone or cortisol given to animals pretreated with estradiol suppressed prolactin binding from 16.4 +/- 4.2% to less than 2.5% after 48-72 h. Parellel results were obtained with 125I labeled human growth hormone whereas 125I labeled-insulin binding was not affected by these treatments. Scatchard analysis showed that the decrease in lactogenic hormone binding was due to a reduced concentration of receptors with no significant change in affinity. Since serum levels of prolactin were not changed, we conclude that treatment with testosterone, medroxyprogesterone, and cortisol decreased lactogenic hormone binding by a direct action on the liver.

Animals↗
PubMed1985

Progesterone has no effect on serum thyroxine-binding globulin concentration in men.

To examine the possible effect of progesterone on circulating T4-binding globulin (TBG) in men, RIA measurements of plasma TBG and T4 levels were made before and after weekly administration of 500 mg medroxyprogesterone acetate, im, to men being treated for paraphilia (sexual deviation syndromes). No change in the mean pretreatment plasma TBG concentration was found after 7-29 days [21.5 +/- 1.2 (+/- SEM) to 22.0 +/- 0.9 microgram/ml; n = 14) or 381-415 days (23.0 +/- 2.5 to 23.1 +/- 2.5 micrograms/ml; n = 5) of medroxyprogesterone treatment. Similarly, the mean pretreatment plasma T4 concentration was unaltered by acute (9.7 +/- 0.6 to 9.7 +/- 0.4 microgram/dl; n = 14) or chronic (11.1 +/- 1.2 to 11.4 +/- 1.0 microgram/dl; n = 5) medroxyprogesterone therapy. We conclude that progestational agents alone do not modify circulating TBG or total T4 concentrations in men.

Adult↗
PubMed2004

Respiratory stimulant use in chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the use of respiratory stimulants in chronic obstructive pulmonary disease (COPD). DATA SOURCES: MEDLINE (1966-July 2003) and EMBASE (1980-3rd quarter 2003) were searched using the search terms medroxyprogesterone acetate, acetazolamide, chronic obstructive pulmonary disease, and chronic obstructive lung disease. DATA SYNTHESIS: Trials are reviewed evaluating ventilatory parameters with acetazolamide and/or medroxyprogesterone in patients with COPD. All studies found improvements in ventilatory parameters, but failed to demonstrate improvements in survival or quality of life. CONCLUSIONS: Significant improvement in arterial blood gas and ventilatory parameters was reported in COPD patients after acetazolamide and medroxyprogesterone treatment; however, with no improvement in survival or quality of life, the place of these drugs in therapy remains unknown.

Acetazolamide↗
PubMed2005

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits.

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 +/- 0.27 to 3.1 +/- 0.20 kg (P = 0.38) between groups at the beginning and 3.1 +/- 0.27 to 3.5 +/- 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 +/- 2.8 and 2.45 +/- 2.1 cm(2), respectively) than the groups receiving no progestogens (G2: 5.6 +/- 4 and G3: 4.6 +/- 2.8 cm(2); P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 +/- 13 and G5: 14.2 +/- 13.4 vs G2: 35.8 +/- 26 and G3: 25 +/- 8 cm(2), respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

Animals↗
PubMed1999

Effects of hormonal contraceptives on bone mineral density.

The clinical research to date on the effects of 3 types of hormonal contraceptives, i.e. depot medroxyprogesterone acetate ('Depo-Provera'), levonorgestrel subdermal implants ('Norplant'), and oral contraceptives, on bone mineral density in premenopausal women is reviewed. The large variance in results across studies for each method is in part due to differences in research design, techniques for measuring bone mineral density, age of the study participants and type of oral contraceptive preparation. However, the balance of the evidence leans toward a positive effect of oral contraceptives on bone mineral density in women of all age. On the other hand, few observations have yet been published on the effects of the new progestin oral contraceptives on bone mineral density. The few extant data suggest a positive impact of levonorgestrel subdermal implants on bone mineral density in women of all ages. Although the findings are preliminary, it appears that depot medroxyprogesterone acetate may exert a negative effect on bone mineral density. More specifically, caution should be exercised in prescribing long term depot medroxyprogesterone acetate (e.g. > 5 years) especially in young adolescents (e.g. < 16 years old) who may not have yet reached peak bone mass.

Adult↗
PubMed2004

Relative cost effectiveness of Depo-Provera, Implanon, and Mirena in reversible long-term hormonal contraception in the UK.

OBJECTIVE: To estimate the relative cost effectiveness for women aged > or =30 years, starting long-term hormonal contraception with either levonorgestrel intrauterine system (Mirena), etonogestrel subdermal implant (Implanon) or medroxyprogesterone acetate injection (Depo-Provera). DESIGN AND SETTING: This was a modelling study, performed from the perspective of the UK NHS, of contraceptive services supplied by a general practitioner. STUDY PARTICIPANTS AND INTERVENTIONS: A dataset was created from the General Practice Research database (GPRD) comprising 16 835 women aged > or =30 years who received levonorgestrel intrauterine system (n = 6080), etonogestrel subdermal implant (n = 277) or medroxyprogesterone acetate injection (n = 10 478) for their long-term contraception between 1997 and 2002. METHODS: Contraception-related healthcare resource utilisation values and contraception continuation rates were obtained from the GPRD. The incidence of pregnancy associated with each contraceptive was obtained from the published literature. By combining the GPRD dataset with published clinical outcomes, a decision model was constructed. This was used to estimate the expected annualised direct healthcare costs and consequences of the provision of each type of contraception per woman-year in pounds sterling (pound) at 2002/03 prices. RESULTS: Our model suggests that starting long-term contraception with levonorgestrel intrauterine system or etonogestrel subdermal implant instead of medroxyprogesterone acetate injection is a dominant strategy from the UK NHS perspective. In contrast, starting long-term contraception with etonogestrel subdermal implant instead of levonorgestrel intrauterine system is likely to be the least cost-effective option, since it would lead to an additional cost for each additional avoided pregnancy (pound 21,000). CONCLUSION: Long-acting reversible hormonal contraception has the benefit of being extremely effective (>99%), and not reliant on patient compliance nor dependent on correct usage. The relative cost effectiveness of using any one contraceptive should be considered in the light of the additional clinical benefits it may confer, user acceptability, QOL, past medical history and the estimated cost of an unintended pregnancy. Choice of contraception is essential to meet diverse user needs and preferences that may change with the user's stage of life. Only by offering choice will the maximum number of women be protected and therefore the greatest savings to the health service be gained.

Adult↗