Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles

Hartard, Manfred; Kleinmond, Christine; Luppa, Peter B.; Zelger, Otto; Egger, K; Wiseman, Michael; Weissenbacher, E. R.; Felsenberg, Dieter; Erben, Reinhold G.

doi:10.1016/j.contraception.2006.06.005

Cited by 29 publications

(20 citation statements)

References 43 publications

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“…Slight differences were noted between COCs containing various different progestins. This observation is supported by another recent prospective study [26], comparing COCs containing the same low-dose of EE, that reported significantly more loss of BMD (71.4%) over 12 months in women on the COC with desogestrel compared with the one containing levonorgestrel and with placebo, neither of which caused changes in BMD. As such, it is one of the few reports showing significant differences between the progestins regarding their effects on bone.…”

Section: Studies In Premenopausal Womensupporting

confidence: 70%

Long-term effects of progestins on bone quality and fractures

Thijssen

2007

Gynecological Endocrinology

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The effects of progestins on the quality of bone and their influence on the risk of fractures are reviewed. Data discussed are based on experimental studies in vivo that generally lasted for longer than one year. Information is given on the background of osteoporosis and on several means of inducing changes in bone quality. In young women who start using oral contraceptives based on progestins alone shortly after pubertal development, a significant decrease in bone quality has been documented. World Health Organization experts have concluded that this is not a real argument for restrictions on the use of these contraceptives. In postmenopausal women, no evidence has been found for a bone-protective or an estrogen-antagonistic effect of progestins. A wide range of estrogens have been used that have shown positive effects on bone, which are not antagonized by progestins. The therapeutic use of high-dose megestrol acetate may result in marked negative effects on bone, leading to severe osteoporosis, possibly due to the inherent glucocorticoid activity of this progestin. Other pharmacotherapeutic agents that can be used in postmenopausal therapy, and that clearly have beneficial effects on bone, are discussed.

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Section: Studies In Premenopausal Womensupporting

confidence: 70%

Long-term effects of progestins on bone quality and fractures

Thijssen

2007

Gynecological Endocrinology

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“…These studies report conflicting results (Bancroft et al ., 1991b; Schaffir, 2006; Graham et al ., 2007; Greco et al ., 2007; Strufaldi et al ., 2010; Caruso et al ., 2011; Battaglia et al ., 2012; Elaut et al ., 2012; Pastor et al ., 2013). Although estrogens have been clearly identified as key hormones for maintaining bone mass (Ott et al ., 2001; Riggs et al , 2002; Ott, 2008), androgens are also important regulators of skeletal growth and maturation (Martel et al ., 1998; Riggs et al , 2002; Hartard et al ., 2006). Data on the effect of androgens in women are scarce but T may exert an effect on protein synthesis and increase muscle mass (Gower and Nyman, 2000; Ružić et al ., 2003).…”

Section: Discussionmentioning

confidence: 99%

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Zimmerman

et al. 2013

Human Reproduction Update

244

151

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BACKGROUNDCombined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.METHODSA review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.RESULTSA total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20–25 µg EE had similar effects on total and free T compared with COCs with 30–35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20–25 µg EE) were found to have less impact on SHBG concentrations.CONCLUSIONSThe current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinica...

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“…Hartard et al [26] compared the skeletal effects of DSG and LNG, both combined with 20 μg of EE, in young women, and found that LNG group did not lose vertebral aBMD, whereas women in the DSG group showed a decrease of − 1.5% at the distal radius and the tibia. LNG induced an increase in total crosssectional area, indicating increased periosteal bone formation.…”

Section: Bone and Progestogensmentioning

confidence: 99%

Bone health in estrogen-free contraception

Hadji

Colli

Regidor³

2019

Osteoporos Int

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Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

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Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles

Cited by 29 publications

References 43 publications

Long-term effects of progestins on bone quality and fractures

Long-term effects of progestins on bone quality and fractures

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Bone health in estrogen-free contraception

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