Research Article| Volume 14, ISSUE 3, P189-199, March 1992

Download started.


Short term effects of SHD 386L and levonorgestrel on bone and mineral metabolism in the postmenopause: a double-blind randomised placebo-controlled trial

      This paper is only available as a PDF. To read, Please Download here.


      Forty-five healthy postmenopausal women participated in a study designed to examine the effects on bone and mineral metabolism of SHD 386L, a new hormone replacement therapy (HRT) regime. This oral preparation delivers 2 mg estradiol valerate daily and 75 μg of levonorgestrel from days 17–28 inclusive of a 28-day cycle. The study was double-blind, randomized and placebo controlled. Patients who received SHD 386L exhibited significant falls in plasma calcium, ionised calcium, phosphate and total alkaline phosphatase. No alteration, however, was observed in plasma osteocalcin. No significant changes in mineral metabolism were observed in a parallel group receiving levonorgestrel alone. The results indicate that SHD 386L is likely to be protective to the skeleton through inhibition of bone resorption and that such actions are attributable to the estrogen component. The preparation was well tolerated, compliance was satisfactory and serious adverse affects were not seen. The above biochemical evidence for skeletal protection will require to be supplemented by prospective biophysical evidence of the effect of SHD 386L on bone mineral density.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Maturitas
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Albright F
        The effects of hormones on osteogenesis in man.
        Rec Prog Horm Res. 1947; 1: 293-359
        • Meema S
        • Bunker ML
        • Meema HE
        Preventative effects of estrogen on bone loss.
        Arch Intern Med. 1975; 135: 1436-1440
        • Horsman A
        • Norden BEC
        • Gallagher JC
        • Kirby PA
        • Milner RM
        • Simpson M
        Observations of sequential changes in bone mass in postmenopausal women: A controlled trial of estrogen and calcium therapy.
        Calc Tissue Res. 1977; 22: 217-224
        • Nachtigall LE
        • Nachtigall RH
        • Nachtigall RD
        • Beckham M
        Estrogen replacement therapy I: A 10 year prospective study in the relationship to osteoporosis.
        Obstet Gynaecol. 1979; 53: 277-281
        • Lindsay R
        • Aitken JM
        • Anderson JB
        • Hart DM
        • MacDonald EB
        • Clarke AC
        Long term prevention of postmenopausal osteoporosis by estrogen.
        Lancet. 1976; i: 1038-1041
        • Weiss NS
        • Ure CL
        • Ballard JH
        • Williams AR
        • Daling JR
        Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen.
        N Engl J Med. 1980; 303: 1195-1198
        • Hutchinson TA
        • Polansky SM
        • Peinstein AR
        Postmenopausal oestrogens protect against fractures of hip and distal radius.
        Lancet. 1979; ii: 705-709
        • Eriksen EF
        • Berg NJ
        • Graham M
        • Colvard DS
        • Mann KG
        • Riggs BL
        Multiple sex-steroid reception in cultured osteoblast-like cells.
        in: International Symposium on Osteoporosis. Abstract 67. SK&F Pharmaceuticals, Denmark1988
        • Pacifici R
        • Civitelli R
        • Rifas L
        • Halstead L
        • Avioli LV
        Does interlukin-I affect intracellular calcium in osteoblast-like cells (UMR-106).
        J Bone Miner Res. 1988; 3: 107-111
        • Aitken JM
        • Armstrong E
        • Anderson JB
        Osteoporosis after oophorectomy in the female rat and the effects of estrogen or estrogen/progestrogen replacement therapy.
        J Endocrinol. 1972; 55: 79-81
        • Lindsay R
        • Hart DM
        • Purdie DW
        • et al.
        Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women.
        Clin Sci Mol Med. 1978; 54: 193-195
        • Dequeker J
        • De Muylder E
        • Ferin J
        The effect of long-term lynestrenol on bone mass in cycling women.
        Contraception. 1977; 15: 717-723
        • Lobo RA
        • McCormick W
        • Singer F
        • Subir R
        Depomedroxy progesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women.
        Obstet Gynaecol. 1984; 63: 1-5
        • Selby PL
        • Peacock M
        • Barkworth SA
        • Brown W
        • Taylor GA
        Early effects of ethinyloestradiol and norethisterone treatment in postmenopausal women on bone resorption and calcium regulating hormones.
        Clin Sci. 1985; 69: 265-267
        • Abdalla HI
        • Hart DM
        • Lindsay R
        • Leggate I
        • Hooke A
        Prevention of bone loss in postmenopausal women by norethisterone.
        Obstet Gynaecol. 1985; 66: 789-792
        • Roof BS
        • Frey D
        • Ross P
        • Lichetenstein L
        • Hudson C
        Increase in postmenopausal women using conjugated estrogen and medroxyprogesterone.
        Clin Res. 1987; 35: 516A
        • Tonelli M
        • Cucinotta D
        • Gnudi A
        Intestinal absorption of radioactive calcium in old patients with osteoporosis treated with medroxyprogesterone acetate.
        G Gerontol. 1970; 18: 420-425
        • Molinis G
        • Bompani R
        • Scali G
        Modifications induced by the treatment with medroxyprogesterone acetate in the urinary excretion of calcium after oral and intravenous load in old subjects.
        G Gerontol. 1970; 18: 361-372
        • Christiansen C
        Bone and progestins.
        in: Int Proc J. 1. 1989: 196-204
        • Eckstein P
        • Whitby M
        • Fotherby K
        • et al.
        Clinical and laboratory findings in a trial of Norgestrel, a low dose progestogen-only contraceptive.
        Br Med J. 1972; 3: 195-200
        • Runnebaum B
        • Rabe T
        New progestogens in oral contraceptives.
        Am J Obstet Gynaecol. 1987; 157: 1059-1063
        • Irisgler K
        • Grabner E
        • Regal H
        Metablische Wirkungen eines Dreistufen-kontraseptivuma.
        in: Hammerstein J Aktuelle Aspekta der Hormoralen Kontrazeption. Excerpta Medica, Amsterdam1982: 65-76
        • Skouby SO
        • Wagner HH
        • Anderson O
        The short term effects of a low dose oral contraceptive on glucose metabolism, plasma lipids and blood clotting factors.
        Contraception. 1983; 28: 489-499
        • Grant RA
        Estimation of hydroxyproline by the autoanalyser.
        J Clin Pathol. 1964; 17: 685-686
        • Rennard SI
        • Berg R
        • Martin GP
        • Foidart JM
        • Robey PG
        Enzyme-linked immunoassay (ELISA) for connective tissue components.
        Ann Biochem. 1980; 104: 205-214
        • Nichols KC
        • Schenkel L
        • Benson H
        17B-Estradiol for postmenopausal estrogen replacement therapy.
        Obstet Gynaecol Surv. 1984; 39: 230-245
      1. Gambrell RDJr. The menopause: benefits and risks of estrogen-progestogen replacement therapy.

        • Hammond CB
        • Jelovsek FR
        • Lee KL
        • Creasman WT
        • Parker RT
        Effects of long term estrogen replacement therapy II. Neoplasia.
        Am J Obstetr Gynaecol. 1979; 133: 537-547
        • Matthews KA
        • Meilahn E
        • Kullar LH
        • Kelsey F
        • Caggiula AW
        • Wing RR
        Menopause and risk factors for coronary heart disease.
        N Engl J Med. 1989; 321: 641-646
        • Bergkvist MP
        • Adami HO
        • Persson I
        • Hoover R
        • Schairer C
        The risk of breast cancer after estrogen and estrogen-progestogen replacement.
        N Engl J Med. 1989; 321: 293-297