ORIGINAL RESEARCH ARTICLE Collagen Metabolism Markers as a Reflection of Bone and Soft Tissue Turnover During the Menstrual Cycle and Oral Contraceptive Use U. Wreje,* J. Brynhildsen,† H. Åberg,* B. Bystro ¨ m,‡ M. Hammar,† and B. von Schoultz‡ Two different groups of women, 23 healthy young adults and 13 women with chronic posterior pelvic pain, were studied before and during use of oral contraceptives (OC). Collagen metabolism markers— here, the amino-terminal propeptide of type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III—as well as hormones and other endo- crine factors indicating the balance between androgen expression/anabolism and catabolism of the subjects (tes- tosterone, sex-hormone binding globulin, and insulin-like growth factor I were measured. Type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III were all signifi- cantly decreased during OC use. These findings implicate OC use-induced changes in collagen type I and III turn- over. A shift in the anabolic/catabolic balance was also recorded indicating a less anabolic situation during OC use. CONTRACEPTION 2000;61:265–270 © 2000 Elsevier Sci- ence Inc. All rights reserved. KEY WORDS: bone metabolism, blood, collagen metabolism, oral contraceptives, menstrual cycle, women Introduction C ombined oral contraceptives (OC) have been widely used by millions of women all over the world for nearly 4 decades. In spite of this length of time and widespread use, the effects of OC use have not yet been thoroughly studied in all physiological systems. Several investigators have studied the effect of OCs on bone mineral density, but the results are contradictory. OC use has been shown to have both long-term beneficial effects 1–4 and no effect 5–7 on bone mineral density in both the pre- and postmenopausal period. At least some of these differ- ent results might derive from the use of different OCs during the different studies. In analogy with the positive effect of estrogen replacement therapy on bone mass in the post-menopausal period, 8 it has been suggested that OC use confers protection against osteoporosis during the later parts of reproductive life. 9 The use of OCs has been recommended in certain groups of women, such as oligomenorrhoic female athletes at high risk for later development of osteoporosis. 9 In a cross-sectional study, Garnero et al. 10 investi- gated bone turnover among OC users and non-users. After studying different collagen metabolites in urine and serum and also bone density, they concluded that bone turnover was decreased during OC use. Bone density was not affected. In a British prospective study, earlier OC users had a higher risk for fractures than earlier non-users. 11 Muscular and skeletal problems are reported to occur more often in OC users than in non-users. 12,13 If bone density is not adversely affected, 1–7 the expla- nation of these findings should lie elsewhere, perhaps in soft tissues such as ligaments and tendons. The main constituent of connective tissue is colla- gen, which appears in different forms. Type I collagen accounts for more than 90 per cent of bone protein contents, but type I is also found in loose connective tissue together with other collagen types. 14,15 Colla- gen type III is found in most dense and loose connec- tive tissue in the body, especially bone marrow, the liver, and the soft tissues. 16 Serum concentrations of the amino-terminal propeptide of type I procollagen (PINP) reflect bone collagen synthesis and correlate well with bone formation rate. 17 The carboxytermi- The study was financially supported by Stockholm County Council, Swedish Medical Research Council, and for the Linkoping part, Swedish Sports Feder- ation and Lions Health Research Foundation. *Department of Clinical Sciences, Division of Family Medicine, Stockholm, Karolinska Institute, Novum, S-14157 Huddinge, Sweden; †Department of Health and Environment, Division of Obstetrics and Gynaecology, Faculty of Health Sciences, Linkoping, Sweden; ‡Department of Women’s Health, Division of Obstetrics and Gynaecology, Karolinska Institute, Stockholm, Sweden Name and address for correspondence: Ullacarin Wreje, Department of Clinical Sciences, Section of Family Medicine, Stockholm, Karolinska Institute, Novum SP-14157 Huddinge, Sweden, +468-58585325; Fax +468-58585305 Submitted for publication October 19, 1999 Revised February 25, 2000 Accepted for publication February 25, 2000 © 2000 Elsevier Science Inc. All rights reserved. ISSN 0010-7824/00/$20.00 655 Avenue of the Americas, New York, NY 10010 PII S0010-7824(00)00106-2