Progesterone or progestin as menopausal ovarian hormone therapy: recent physiology-based clinical evidence Effect of gonadotropin-releasing hormone agonist on the bone mineral density of patients with endometriosis. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. Differential effects on bone density of progestogen-only methods for contraception in premenopausal women. Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. Bone Mineral Density and Endogenous Hormones and Risk of Breast Cancer in Postmenopausal Women (United States) A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis. Reproductive hormones and skeletal health in young women. Bone mineral density is not significantly reduced in adult patients on low-dose glucocorticoid replacement therapy. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Hormone replacement therapy and the prevention of postmenopausal osteoporosis [Relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density of Chinese postmenopausal women]. Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea – preliminary study [The effect of primary lack of estrogens and the influence of the age at the beginning of estrogen therapy on bone mineral density in patients with Turner's syndrome].
Purpose of review Provide evidence -based recent data on oral micronized progesterone ( OMP ) and progestins in menopausal hormonal therapy ( MHT ) . Recent findings Medroxyprogesterone acetate ( MPA ) increases breast cancer acting through the glucocorticoid receptor ; progestins in MHT increase thrombosis more than oral estrogens ; MPA , but not OMP or other progestins , increase monocyte cell endothelium adhesion ; MPA and estradiol (E2)/MPA have negative brain effects , whereas E2/progesterone ( P4 ) has neuroregenerative brain effects . The ‘ window of opportunity ’ cardiovascular disease hypothesis is not supported by a r and omized controlled trial showing that transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media thickness ; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome ;  transdermal estradiol/OMP does not increase venous thromboembolism in observational data . P4 decreases breast cell proliferation and improves prognosis through P4 receptor alteration of estrogen receptor & agr ; genetic effects ;  OMP with conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospect i ve cohorts , one population -based . Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day . Summary New data show CEE/E/E2+MPA/P mechanisms for negative breast cancer , venous thromboembolism , cardiovascular system , and brain effects .  OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT syndrome .  OMP effectively treats vasomotor symptoms and sleep disturbances , and could safely be used alone for symptomatic menopause OBJECTIVE To examine changes in bone mineral density ( BMD ) of patients treated with GnRH agonist ( GnRH-a ) by dual-energy X-ray absorptiometry and to underst and factors related to bone loss . DESIGN Prospect i ve controlled trial examining BMD during and after GnRH-a therapy every 24 weeks for 18 months in patients with endometriosis compared with nontreated controls . SETTING Out patients clinic at a university hospital and its affiliated outpatient clinic . PATIENTS Twenty-two patients with endometriosis as GnRH-a-treated group , 12 healthy women with normal menstrual cycle , and 7 patients with mild endometriosis as control group . INTERVENTIONS Patients were treated with a GnRH-a ( buserelin acetate ) at 900 micrograms/d by nasal spray for 24 weeks . RESULTS The significance of differences in change-rates at all measured points in both groups was assessed by analysis of variance . The interaction between treatment and period was significant , and only week 24 of the GnRH-a-treated group was significantly lower compared with baseline . The reduction rate of BMD was high in patients 33 years of age or younger compared with those who were 34 years of age or older . According to a multiple-regression model , the most important factor related to bone loss was the post-treatment serum levels of E2 . CONCLUSION At the end of treatment , BMD was significantly lower than that of the control group , and the reduction rate was 3.4 % . A factor related to bone loss was degree of ovarian suppression OBJECTIVE To assess the effects of hormone therapy on bone mineral density ( BMD ) in the spine and hip of postmenopausal women . DESIGN A 3-year , multicenter , r and omized , double-blinded , placebo-controlled clinical trial . PARTICIPANTS A total of 875 healthy women aged 45 to 64 years recruited at 7 clinical centers . INTERVENTIONS Treatments were ( 1 ) placebo ; ( 2 ) conjugated equine estrogens ( CEE ) , 0.625 mg/d ; ( 3 ) CEE , 0.625 mg/d plus medroxyprogesterone acetate ( MPA ) , 10 mg/d for 12 d/mo ; ( 4 ) CEE , 0.625 mg/d plus MPA , 2.5 mg/d daily ; or ( 5 ) CEE , 0.625 mg/d plus micronized progesterone ( MP ) , 200 mg/d for 12 d/mo . MAIN OUTCOME MEASURES Bone mineral density at baseline , 12 months , and 36 months . RESULTS Participants assigned to the placebo group lost an average of 1.8 % of spine BMD and 1.7 % of hip BMD by the 36-month visit , while those assigned to active regimens gained BMD at both sites , ranging from 3.5 % to 5.0 % mean total increases in spinal BMD and a mean total increase of 1.7 % of BMD in the hip . Changes in BMD for women assigned to active regimens were significantly greater than those assigned to placebo . Women assigned to CEE plus continuous MPA had significantly greater increases in spinal BMD ( increase of 5 % ) than those assigned to the other 3 active regimens ( average increase , 3.8 % ) . Findings were similar among those adhering to assigned therapy , although , among adherent participants , there were no significant differences in BMD changes among the 4 active treatment groups . Older women , women with low initial BMD , and those with no previous hormone use gained significantly more bone than younger women , women with higher initial BMD , and those who had used hormones previously . CONCLUSIONS Postmenopausal women assigned to placebo demonstrated decreased BMD at the spine and hip , whereas women assigned to estrogen therapy increased BMD during a 36-month period . These findings demonstrate that estrogen replacement therapy increases BMD at clinical ly important sites CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P<.001 ) . The HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed . Data from a prospect i ve r and omized clinical trial among 22 premenopausal women , age 32.6 ( range 20 - 45 years ) , who were r and omly assigned to either of two treatments with continuous progestogens for contraception were analyzed ; depot-medroxyprogesterone acetate ( DMPA ) or continuous levonorgestrel treatment with subdermal implants ( Norplant ) , respectively . Forearm bone density ( BMDprox ) increased with 2.94 % ( p = 0.006 ) in women who were prescribed levonorgestrel , which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate ; group difference at 6 months for BMDprox 3.4 % ( 95 % CI 1.3 , 5.5 ; p = 0.025 ) and BMDdist 4.1 % ( 95 % CI - 1.3 , 9.6 ; p = 0.077 ) . The changes in bone density were consistent with the changes in biochemical indices for bone metabolism ;  DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase ( p = 0.004 ) and osteocalcin ( p = 0.007 ) . The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA , in st and ard clinical doses for contraception In women , the influence of and rogens on bone health is not clear . It has been suggested that the and rogen receptor ( AR ) genotype is associated with bone mineral density and serum and rogen levels in pre- and perimenopausal women , but the association between AR genotype , bone mineral density , and fracture risk has not been studied in postmenopausal women . Therefore , we studied whether AR polymorphism affects bone mineral density , bone mineral density change , or fracture risk in a 5-year r and omized hormone replacement therapy ( HRT ) trial on 331 early postmenopausal women ( mean baseline age , 52.7 + /- 2.3 years ) . The participants consisted of two treatment groups : the HRT group ( n = 151 ) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3 , 100 - 300 IU + 93 mg calcium as lactate/day , and the non-HRT group ( n = 180 ) received 93 mg calcium alone or in combination with vitamin D3 , 100 - 300 IU/day for 5 years .  Bone mineral density was measured from lumbar spine and proximal femur ( DXA ) before and after the 5-year trial . All new symptomatic , radiographically defined fractures were recorded during the follow-up . The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction ( PCR ) amplification . The subjects were divided into three repeat groups according to AR alleles . None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment . The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT ( p = 0.926 and 0.146 , respectively ) or non-HRT ( p = 0.818 and 0.917 , respectively ) groups . In all , 28 women sustained 33 fractures during the follow-up . Thus , the numbers of fractures were limited . The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups ( p = 0.632 and 0.459 , respectively ; Cox proportional hazards model ) . In conclusion , AR gene polymorphism was not associated with baseline bone mineral density , 5-year bone mineral density change , or fracture risk in early postmenopausal Finnish women Objective : This case – cohort study was design ed to examine whether total hip bone mineral density ( BMD ) is independently associated with breast cancer over and above its association with other determinants , including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin . Methods : Our study population was selected from a cohort of 8203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992 , at which time  BMD was assessed  , and  blood sample s were obtained . A total of 109 women developed breast cancer during four years of follow-up ; 173 other r and omly selected women from the larger cohort were also selected . Cox proportional hazards with robust variance adjustment was used for these analyses . Results : Relative to women in the lower fourth of the BMD distribution , the risk associated with being in the upper fourth was 2.6 ( 95 % confidence interval ( CI ) 1.1–5.8 ) . After adjusting for serum hormone levels , the corresponding relative risk was 2.5 ( 95 % CI 0.9–5.2 ) . With body mass index and number of years since menopause added to the multivariate analysis , the relative risk decreased to 1.4 ( 95 % CI 0.5–4.0 ) . Conclusions : BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates PURPOSE Hormone replacement therapy ( HRT ) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density ( BMD ) in postmenopausal women . This 4-year prospect i ve r and omized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis . PATIENTS AND METHODS Seventy-two postmenopausal women ( mean age 64.9+/-0.5 years ) attending metabolic bone disease outpatient clinics with established osteoporosis were r and omly allocated into one of four treatment groups and monitored for 4 years . All patients enrolled in this study including the control group ( n=18 ) received 1.0 g elemental calcium and 400 units vitamin D per day . The HRT group ( n=18 ) received cyclical estrogen and progesterone ; the etidronate group ( n=17 ) received intermittent cyclical etidronate ; and the combined therapy group ( n=19 ) received both HRT and etidronate .  BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment . Changes in height were recorded , and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation . In 40 patients ( 10 patients per group ) , analysis of bone histomorphometry was carried out after 4 years of treatment . RESULTS In patients who received the combined therapy , BMD increased in the lumbar spine by 10.4 % ( P < 0.001 ) and in the hip by 7.0 % ( P < 0.001 ) at 4 years . For patients treated with ICE , these increases were 7.3 % ( P < 0.001 ) and 0.9 % ( P < 0.05 ) , and with HRT , the increases were 7.0 % ( P < 0.001 ) and 4.8 % ( P < 0.01 ) in the vertebrae and femora , respectively . The group treated with calcium and vitamin D lost 2.5 % ( P < 0.05 ) and 4.4 % ( P < 0.01 ) of BMD in the vertebrae and femora , respectively , after 4 years . Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora ( P < 0.05 ) in comparison with patients who were treated with HRT or etidronate alone after 4 years . In comparison with patients in the control group , there was a trend toward a lower rate of new vertebral fractures in the treatment groups . Height loss was significantly less in all three active treatment groups ( HRT [ P < 0.001 ] , etidronate [ P < 0.02 ] , and combined therapy group [ P < 0.0001 ] ) , in comparison with the control group . The combined therapy group did not have a significant height loss , in comparison with the HRT ( P < 0.02 ) and the etidronate ( P < 0.001 ) groups . None of the patients had histomorphometric evidence of osteomalacia . CONCLUSION This 4-year r and omized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis In young women , low estrogen levels complicate a wide variety of diseases , including premature ovarian failure , anorexia nervosa , athletic amenorrhea , prolactinoma , hypopituitarism , and chronic kidney disease . Hypoestrogenemia may also result from therapy with GnRH agonists , glucocorticosteroids , chemotherapy , and especially aromatase inhibitors . All of these situations are associated with bone loss , because estrogen chronically suppresses bone resorption . Several mechanisms are involved : 1 ) estrogen increases osteoclast apoptosis ; 2 ) by suppressing interleukins and proinflammatory cytokine expression in bone marrow cells , estrogen decreases the number of osteoclasts ; 3 ) by inhibiting the production of receptor activator of nuclear factor-κB lig and , estrogen reduces the number and activity of osteoclasts ; and 4 ) by increasing stromal cell/osteoblast cell expression of TGFβ , estrogen inhibits osteoclast activity . Estrogen also has some positive effects on bone formation by acting as a mitogen to cells early in the osteoblast line , reducing apoptosis of osteoblasts , and increasing expression of TGFβ , bone morphogenetic proteins , and IGF-I ( 1 ) . In these pathological conditions , the cause of the bone loss is frequently multifactorial . For example , women with anorexia nervosa also have low IGF levels . Nonspecific factors such as poor diet , reduced exercise , or chronic inflammation may further increase bone resorption . Low estrogen levels are also seen in healthy young women who are using depo-medroxyprogesterone acetate ( DMPA ) for contraception .  Bone loss is a side effect of this medication ( 2 ) . The bone mineral density ( BMD ) decreases at a more rapid rate during the first years of therapy and then continues to decrease at a slower rate ( 3 ) . After 5 yr , the loss is about 6 % ( 0.5 sd ) . The  DMPA effects are worse in teenagers ; combined results from four prospect i ve studies found an average loss of spine BMD of 3.1 % over 2 yr in  DMPA  users compared with a gain of 7.2 % in untreated controls ( 4 ) . A cross-sectional study in this issue by Walsh and colleagues ( 5 ) focused on the age of starting DMPA .  One group aged 18–25 started DMPA before age 20 , and another group aged 35–45 started after age 34 . Each group had matched controls . Importantly , the average use was 37 months in both groups . This avoids the confounding between age and duration of use , which is encountered in other studies . The BMD was significantly lower than controls when DMPA was started in teenagers but not when it was started after age 34 . Estrogen levels were lower in the DMPA users than the non-hormone users and were also lower in the younger women than in the older women . The authors concluded that estrogen levels mediated the effect of DMPA on bone markers because adding DMPA to a regression model reduced the correlation between markers and estrogen . These correlations were not very strong ( r = −0.17 between N-telopeptide and estradiol-treated ) , so this is a tenuous conclusion , but it is bolstered by the findings from two other studies that adding estrogen to DMPA abolishes the negative effect on the skeleton ( 6,7 ) . The age range of the older group of women is underrepresented in most of the previous studies of skeletal effects of DMPA . These results lead to several questions about basic bone biology . How are adolescent bones different from mature bones ? How does DMPA use compare to the natural state of low estrogen seen in healthy lactating women ? Is bone completely restored in these situations ? There are also important clinical questions about potential risk of fractures and the skeletal risks from other forms of contraception CONTEXT Patients with primary adrenal insufficiency ( PAI ) and patients with congenital adrenal hyperplasia ( CAH ) receive glucocorticoid replacement therapy , which might cause osteoporosis . OBJECTIVES Questions addressed by this study were : 1 ) Is bone mineral density ( BMD ) reduced in PAI and CAH on lower glucocorticoid doses than previously reported ? 2 ) Is BMD in PAI influenced by the type of glucocorticoid used ? and 3 ) Does DHEA treatment affect BMD in PAI women ? DESIGN AND PATIENTS We conducted a prospect i ve , cross-sectional study including 81 PAI patients and 41 CAH patients . MAIN OUTCOME MEASURES BMD was measured by dual-energy x-ray absorptiometry .  Serum levels of bone turnover markers , minerals , vitamins , hormones , and urinary crosslinks were measured . RESULTS PAI and CAH patients received average daily hydrocortisone doses of 12.0 ± 2.7 mg/m(2 ) ( range , 4.9 - 19.1 ) and 15.5 ± 7.8 mg/m(2 ) ( range , 5.7 - 33.7 ) , respectively . BMD varied within the normal reference range ( -2 to + 2 ) in both cohorts . However , lower Z-scores for femoral neck and Ward 's region were found in CAH compared to PAI women , but not in men . Prednisolone treatment showed significant lower osteocalcin levels and lower Z-scores for lumbar spine and femoral neck compared to PAI patients on hydrocortisone . PAI women treated with DHEA had significantly lower urinary collagen crosslinks and bone alkaline phosphatase , and significantly higher Z-scores in lumbar spine and femoral Ward 's region compared to non-DHEA-treated women . CONCLUSIONS Adult PAI and CAH patients on low glucocorticoid doses showed normal BMD within the normal reference range . The use of longer acting prednisolone result ed in significantly lower BMD in PAI . In addition , DHEA treatment may have a beneficial effect on bone in Addison 's women CONTEXT Lower-than-commonly-prescribed doses of conjugated equine estrogens ( CEEs ) with medroxyprogesterone acetate ( MPA ) improve vasomotor symptoms and vaginal atrophy , provide acceptable bleeding and lipid profiles , and afford endometrial protection . This lower-dose therapy 's protection against loss of bone mineral density ( BMD ) associated with menopause has not been thoroughly investigated . OBJECTIVE To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD , total body bone mineral content ( BMC ) , and biochemical markers of bone turnover in postmenopausal women . DESIGN AND SETTING Two-year r and omized , double-blind , placebo-controlled sub study of the Women 's Health , Osteoporosis , Progestin , Estrogen trial , conducted at 19 US centers between August 1995 and October 2000 . PARTICIPANTS Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period . INTERVENTIONS Patients were r and omly assigned to receive CEEs , 0.625 ; CEEs , 0.625 and MPA , 2.5 ; CEEs , 0.45 ; CEEs , 0.45 and MPA , 2.5 ; CEEs , 0.45 and MPA , 1.5 ; CEEs , 0.3 ; CEEs 0.3 and MPA , 1.5 ( all doses in mg/d ) ; or placebo for 2 years . All participants also received elemental calcium at 600 mg/d . MAIN OUTCOME MEASURES Changes from baseline in spine and total hip BMD , total body BMC , and biochemical markers of bone turnover ( serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen ) , assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach . RESULTS At 24 months , women assigned to all of the active treatment groups had significant gains from baseline ( P<.001 ) in spine and hip BMD and total body BMC ( except total body BMC in the group receiving CEEs , 0.3 mg/d ) . These changes were significantly different from those in the placebo group , in which losses of bone mass in spine and total body were evident over the course of the study ( P<.001 ) . The loss in hip BMD from baseline in the placebo group was significant at 18 ( P = .02 ) but not at 24 months ( P = .06 ) . Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline ( P<.001 ) for all active treatment groups at all time points ; no changes were found for the placebo group . For women treated with CEEs alone , the gains in spine BMD for the group taking CEEs , 0.625 mg/d , were significantly higher than those of the group taking CEEs , 0.3 mg/d ( P = .02 ) , but not the group treated with CEEs , 0.45 mg/d ( P = .48 ) . CONCLUSIONS Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women BACKGROUND Hormone replacement therapy ( HRT ) , the mainstay of osteoporosis prevention , is limited because of dose-related risks , side effects , and patient acceptance . The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women . OBJECTIVE To determine the bone-sparing effect of continuous low-dose HRT in elderly women . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING University osteoporosis research and clinical center . PATIENTS 128 healthy white women ( age > 65 years ) with low bone mass recruited by word of mouth and by local advertisement . The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less . INTERVENTION Continuous therapy with conjugated equine estrogen , 0.3 mg/d , and medroxyprogesterone , 2.5 mg/d , or matching placebo . Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups ; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups . MEASUREMENTS Bone mineral density of the spine , hip , total body , and forearm ; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals ; and 24-hour urine creatinine and hydroxyproline excretion at baseline , 12 months , and 42 months . RESULTS During 3.5 years of observation , spinal bone mineral density increased by 3.5 % ( P < 0.001 ) in an intention-to-treat analysis and by 5.2 % among patients with greater than 90 % adherence to therapy . Significant increases were seen in total-body and forearm bone density ( P < 0.01 ) . Symptoms related to HRT  ( breast tenderness , spotting , pelvic discomfort , and mood changes ) were mild and short-lived . CONCLUSIONS Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other , higher-dose HRT regimens in elderly women . This combination is well tolerated by most patients Fracture prevention is one of the public health priorities worldwide . Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis , the most common metabolic bone disease . Different effective treatments for osteoporosis are available . Hormone replacement therapy ( HRT ) at different doses rapidly normalizes turnover , preserves bone mineral density ( BMD ) at all skeletal sites , leading to a significant , reduction in vertebral and non-vertebral fractures .  Tibolone , a selective tissue estrogenic activity regulator ( STEAR ) , is effective in the treatment of vasomotor symptoms , vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT . Selective estrogen receptor modulators ( SERMs ) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures . The combination of bazedoxifene and conjugated estrogens , defined as tissue selective estrogen complex ( TSEC ) , is able to reduce climacteric symptoms , reduce bone turnover and preserve BMD . In conclusion , osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms . The use of a st and ard dose of HRT for osteoporosis prevention is based on biology , epidemiology , animal and pre clinical data , observational studies and r and omized , clinical trials . The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover , with compelling scientific evidence OBJECTIVE To investigate the relationship between estrogen receptor gene Px haplotype and the effect of calcium and soy isoflavone supplementation on bone mineral density ( BMD ) of Chinese postmenopausal women . METHODS It was a r and omly controlling test for 12 months . The Pvu II and Xba I polymorphisms of ER-alpha gene were detected by using restriction fragment length polymorphisms ( RFLP ) in 691 Chinese postmenopausal women , aged 45 - 65 years . In 497 carriers of definitive Pvu II-Xba I haplotype , 93 subjects were chosen r and omly . BMD was measured by dual energy X-ray absorptiometry ( DXEA ) . According to BMD T score in any skeleton site of 81 subjects at baseline , 29 subjects with T > or = -1.5 were grouped into observation group , and 52 subjects with T < -1.5 were r and omly assigned into two intervention groups and received either a 100 mg soy isoflavone and 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) or 440 mg Ca and 100 IU VD supplement/d ( n = 26 ) . BMD of the whole body , lumber ( L2-L4 ) , and hip were measured at baseline and after 12 months . RESULTS After one year fellow-up , the BMD at L2-L4 , femur neck site and whole body were significantly decreased as compared with those of baseline ( P < 0.05 , change percent of BMD as follows : -3.31 % , -3.09 % , -1.88 % ) in observation group , and the whole body BMD was significantly lower at 12 month than that at baseline in subjects with Px haplotype ( percent change was -2.44 % , P < 0.05 ) , but no difference was found in subjects without Px haplotype . Whole body and femur neck BMD were significantly decreased in both Ca group and Ca + soy isoflavone group , but no significant difference of change percent between two groups . There were no significant changes in L2-L4 and trochanter BMD irrespective of treatment . ER-alpha Px haplotype had no effect on the changes in BMD in both Ca group and Ca + soy isoflavone group . CONCLUSION The rate of bone loss in Chinese postmenopausal women seems to haverelation to ER Px haplotype . Calcium supplementation for 1 year might lower the bone loss rate , but soy isoflavone supplementation for 1 year had notshowu no effects . The effect of supplementation had no relationship with ER Px haplotype Ovarian failure after allogeneic stem cell transplant ( allo-SCT ) is an important risk factor for development of osteoporosis . We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT . A total of 60 women with osteoporosis or osteopenia were divided r and omly into four groups of 15 women each . Group 1 was treated with calcium and vitamin D alone , group 2 received the same treatment in combination with hormone replacement therapy ( HRT ) , group 3 received risedronate ( 35 mg weekly , orally for 1 year ) and group 4 zoledronic acid ( 3 monthly doses of 4 mg ( intravenous ) ) . All groups were similar for age , body mass index , underlying disease and time elapsed from transplant . Lumbar and femoral bone mineral density ( BMD ) were measured at baseline and after 12 months , together with serum osteocalcin and urinary hydroxyproline . At 12 months , a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2 . Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck . Zoledronic acid increased significantly both lumbar and femoral BMD . In groups 3 and 4 the hydroxyproline excretion was significantly reduced , while osteocalcin mildly increased only in group 4 . In conclusion , bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT Introduction The aim of this study was the long-term prospect i ve evaluation of the effects of estroprogestagen ( EP ) therapy on the bone mineral density ( BMD ) of girls with functional hypothalamic amenorrhea ( FHA ) carrying various PvuII and XbaI polymorphisms of ER-α . Material and methods Prospect i ve observation included 84 FHA girls and 50 controls . The FHA patients were subjected to 4-year sequential therapy with 17β estradiol ( 2 mg from the 2nd to 25th day of the menstrual cycle ) and dydrogesterone ( 10 mg from the 16th to the 25th day ) . Hormonal parameters , serum concentration of the bone fraction of alkaline phosphatase ( BALP ) , urine concentration of cross-linked n-telopeptide of type I collagen ( Ntx ) and BMD were determined before and after the treatment . Results Six-month treatment result ed in a marked increase in estradiol ( p = 0.001 ) , testosterone and prolactin levels ( p = 0.01 both ) and a significant decrease in BALP and Ntx ( p = 0.001 both ) . Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII ( p = 0.003 ) . A significant increase in BMD was observed throughout the entire therapy period , with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α . Conclusions The EP therapy is effective in the treatment of BMD disorders associated with FHA , and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α Lumbar spine bone mineral density ( BMD ) values were measured in women with Turner 's syndrome ( TS ) and the influence of primary ovarian failure as well as the age at the start of estroprogestins ( EP ) therapy were considered . EP treatment with 2 mg of estradiol ( E2 ) and BMD monitoring were started in 72 and finally continued for 5 years in 34 patients with TS , aged 12 - 38 years , previously not treated with growth hormone or anabolic steroids .  The mean total BMD gain ( deltaBMD ) was 20 % and the most significant increase was observed after the first ( 7.5 % ) and the second ( 6.6 % ) year of the therapy . Before the start and during EP treatment E2 levels were evaluated : they increased from 9.2pg/ml to the values observed in the controls ( C ) but positive correlation with BMD was not observed . Analysis of TS patients in age brackets ( < 15 years , 15 - 20 years , 21 - 25 years , > 25 years ) showed that only in the group that started EP treatment before the age of 15 every year significant deltaBMD was observed . The group that started EP therapy after the age of 20 did n't achieve significant deltaBMD . Patients wit TS had significantly higher levels of bone metabolism markers ( Ntx and BALP ) than the controls and in both groups negative correlation with age was found . On the basis of the results the conclusion was made that in hypoestrogenic women , not exclusively TS , the age when estrogen therapy is started may determine the effects in relation to bone mass . The administered E2 doses may also be important
CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related  increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy .