Cyclic medroxyprogesterone treatment increases bone density: A controlled trial in active women with menstrual cycle disturbances

Prior, Jerilynn C.; Vigna, Yvette M.; Barr, Susan I.; Rexworthy, Cori; Lentle, Brian C.

doi:10.1016/0002-9343(94)90092-2

Cited by 135 publications

(82 citation statements)

References 27 publications

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“…Specifically, adolescent girls with oligomenorrhea and amenorrhea, whether linked (56) or not (57) to exercise or eating disorders, are at risk for osteopenia. Interestingly, cyclic treatment with a progestative (medroxyprogesterone) to mimic normal cycles in women with irregular cycles may increase bone density (58). These preliminary data suggest that not only estrogen per se but also an optimal ratio of estrogen to progesterone could significantly help prevent osteoporosis in premenopausal women.…”

Section: Deleterious Health Consequences Of Gonadal Imbalancementioning

confidence: 90%

Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

Brucker‐Davis

Thayer

Colborn

2001

Environ Health Perspect

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We review the significant and adverse health effects that can occur with relatively small endogenous hormonal changes in pubertal and adult humans. We discuss the effects of hormonal changes that occur within normal physiologic ranges--such as the rising levels of estrogen in peripuberty, which cause growth spurts at low levels and then the fusion of epiphyses at higher levels--and the hormonal variations during the menstrual cycle and their relation to genital phenotypic changes and intercurrent disease evolution. We turn next to adaptive changes in gonadal and other functions during aging, exercise, stress, starvation, and chronic diseases, which can serve as models for the effects of exogenous, hormonally active compounds. Then we review the states of borderline hormonal imbalances such as subclinical (having few or very mild symptoms, if any) hypothyroidism or hyperthyroidism, glucose intolerance, and other endocrine conditions. Finally, we review the deleterious systemic effects of gonadal imbalance. Information stemming from clinical observations leads to the concept of "no threshold" within the endocrine system and thus illustrates the importance of considering low-dose testing for chemicals that interfere with hormonal activity. We also urge attention to more sensitive, less visible end points such as osteoporosis, increased risk for cardiovascular disease, or cognitive changes.

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Section: Deleterious Health Consequences Of Gonadal Imbalancementioning

confidence: 90%

Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

Brucker‐Davis

Thayer

Colborn

2001

Environ Health Perspect

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“…(25,26) P appears also to inhibit bone resorption by mature osteoclasts isolated from rat long bones in a dose dependent manner (27) and pharmacological doses of progestagens decrease the urinary output of calcium and Hyp in humans. (28) Cyclic medroxyprogesterone increases spine BMD in women with abnormal menstrual cycles (29) and estrogen/progesterone replace- …”

Section: Discussionmentioning

confidence: 99%

“…ment therapy prevents bone loss in postmenopausal women. (29)(30)(31) The purpose of this study was to determine if the cyclic changes of female sex hormones that occur during the menstrual cycle are related to changes in bone resorption or formation as reflected by serum and urine markers of those functions.…”

Section: Figmentioning

confidence: 99%

Changes in Bone Resorption During the Menstrual Cycle

Chiu

Mayes³

et al. 1999

Journal of Bone and Mineral Research

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To determine if the cyclic changes of female sex hormones during the menstrual cycle are related to changes in bone formation and resorption, we measured serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) and bone resorption markers, serum and urine deoxypyridinoline (Dpyr), three times per week during one menstrual cycle in 20 healthy premenopausal women. Serum estradiol (E 2 ) and progesterone (P) showed characteristic cyclic fluctuations. Serum Dpyr was higher during the follicular phase (

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“…In human osteoblasts both isoforms of PR are expressed, and estrogen induced both A and B promoters (74). Progestins have been found to stimulate osteoblast proliferation, differentiation, and growth factor expression (25, 26, 76 -80) and to increase bone formation (81,82). In ovariectomized dogs, PG increased bone formation (83) and in postmenopausal women progestins combined with estrogen increased bone density to a greater extent than estrogen alone (84,85).…”

Section: Discussionmentioning

confidence: 99%

Progesterone Stimulation of Human Insulin-like Growth Factor-binding Protein-5 Gene Transcription in Human Osteoblasts Is Mediated by a CACCC Sequence in the Proximal Promoter

Boonyaratanakornkit

Strong

Mohan

et al. 1999

Journal of Biological Chemistry

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Insulin-like growth factor-binding protein-5 (IGFBP-5)is produced by osteoblasts and potentiates insulin-like growth factor mitogenic stimulation in osteoblast cell cultures. Progesterone (PG) increased IGFBP-5 expression in normal human osteoblasts and increased IGFBP-5 transcription in U2 human osteosarcoma cells. We developed a chloramphenicol acetyltransferase reporter construct containing the human IGFBP-5 proximal promoter sequence, which includes TATA and CAAT boxes, and five putative PG response element half-sites. 10 ؊8 M PG increased promoter activity of this construct in U2 cells co-transfected with a PG receptor isoform A (PR A ) expression vector. Analysis of 5 deletion constructs indicates that PG transactivation of IGFBP-5 promoter activity does not require the PG response element half-sites but does require the region ؊162 to ؊124 containing two tandem CACCC box sequences. Mutation of the proximal CACCC box at ؊139 eliminated PG transactivation. Gel shift assays using a ؊162 to ؊124 DNA fragment, U2 cell nuclear extracts, and purified PR A protein indicate that nuclear factors bind to a CACCC sequence at ؊139 and that PR A alters the pattern of transcription factor interaction with the CACCC sequence. Using a luciferase reporter construct containing base pairs ؊252 to ؉24 of the IGFBP-5 promoter, we found that both PR A and PR B isoforms mediated PG stimulation of promoter activity. These results suggest that PG may stimulate IGFBP-5 gene transcription via a novel mechanism involving PR and CACCC-binding factors.Insulin-like growth factor-binding protein-5 (IGFBP-5) 1 belongs to a family of six structurally related proteins that are unrelated to the IGF receptors and that bind IGF-I and IGF-II with high affinity (1-3). IGFBPs modulate the mitogenic and metabolic activities of the IGFs in vitro, suggesting an important role in IGF physiology in vivo. Of the various IGFBPs, IGFBP-5 is unique in that it stimulates IGF-induced osteoblastic cell proliferation when added simultaneously with IGF I or II to serumfree osteoblast-like cell cultures (4 -7). Recent evidence suggests that IGFBP-5 may stimulate cell proliferation by an IGF-independent mechanism involving IGFBP-5 specific cell surface binding sites (7,8). In addition, IGFBP-5 binds with high affinity to hydroxyapatite and to various extracellular matrix proteins, properties that are consistent with a role for this binding protein in fixing IGFs to extracellular matrices including mineralized bone (7, 9, 10). IGFBP-5 may be a more potent enhancer of IGF activities when bound to extracellular matrix than in solution (10). Coding sequences and 5Ј-flanking regions of IGFBP-5 genes are highly conserved in human, rat, and mouse (4, 5, 11-13), and the mouse and human 5Ј-flanking regions have been found to impart basal promoter activity to reporter gene constructs in several cell types, including osteoblasts (12-16).IGFBP-5 is expressed by a number of cell types including fibroblasts, myoblasts, and osteoblasts, and production of IG-FBP-5 is regulated ...

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Cyclic medroxyprogesterone treatment increases bone density: A controlled trial in active women with menstrual cycle disturbances

Cited by 135 publications

References 27 publications

Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

Significant effects of mild endogenous hormonal changes in humans: considerations for low-dose testing.

Changes in Bone Resorption During the Menstrual Cycle

Progesterone Stimulation of Human Insulin-like Growth Factor-binding Protein-5 Gene Transcription in Human Osteoblasts Is Mediated by a CACCC Sequence in the Proximal Promoter

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