Original research articleShort-term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 μg of ethinyl estradiol: Observational study in young postadolescent women
Introduction
The bone mineral density (BMD) is reduced in women with low ovarian estrogen levels due to hypothalamic amenorrhea [1], [2], [3] or to premature ovarian failure [4] or to GnRHa- chronic treatment [5]. However, low ovarian estrogen levels due to use of oral contraceptives (OCs) containing estrogen-progestin formulations do not seem to cause impairment to bone metabolism in young postadolescent women [6], even when formulations with low [7], [8], very low [7], [9], [10] or ultra-low doses [10] of ethinyl estradiol (EE) are used.
On the contrary, some studies concur to show that contraceptive treatment with only progestagen compounds derived from 17-OH progesterone [11], but not from 19-nor testosterone [11], [12], [13], could impair bone health. Therefore, the effect of an OC on the bone could depend not only on EE content, but also on the pharmacological properties of the progestin compound [11]. The residual androgenic affinity of synthetic 19-nor-testosterone derivatives could protect bone health through a direct effect on androgen osteoblast receptors [14], [15]. It is also known that the androgenic activity of these steroids could increase androgenic availability because they counteract the stimulatory effect of EE on hepatic sex hormone-binding globulin (SHBG) secretion [16], [17]. Furthermore, it has been shown that 19-nor-testosterone derivatives exert estrogenic effect through the estrogen receptors [18].
Drospirenone (DRSP) is a 17-α-spirolactone derivative with pharmacological properties that uniquely combine progestogenic, antimineralcorticoid and antiandrogenic activity but without estrogenic and androgenic activity [19], [20], [21]. The OC containing 3 mg DRSP plus 30 μg EE (DRSP+EE) proved to provide effective oral contraception, excellent cycle control and good tolerability, mainly because DRSP counteracts water retention related to EE and improves psychological symptoms with a global positive effect on the woman's well-being [22]. A recent study by our group [23] suggests that DRSP+EE could also improve anxiety, and other psychological symptoms in a population of healthy women without psychological diseases and without premenstrual symptoms.
Even though it has been shown that the addition of spironolactone to different OCs treatments does not impair bone turnover [24], no studies have been published up to now on the role of DRSP+EE on bone metabolism. This study aimed to assess whether variations of BMD and biochemical markers of bone formation and bone resorption occur during a 6-month treatment with DRSP+EE in young postadolescent women.
Section snippets
Subjects
The subjects included in the study were recruited from women who presented to the Department of Obstetrics and Gynaecology of the University of Cagliari asking for contraception. Subjects included in the study did not have contraindications to OC intake in accordance with the World Health Organization guidelines [25]. They did not have past or present bone diseases, disorders of bone metabolism, thyroid diseases, disorders of lipid or glucose metabolism, renal, hepatic or urinary diseases or a
Results
Two women in the control group did not complete the study for personal reasons, whereas no woman in the OC group abandoned the study. Therefore, all results are reported as mean ± SD for 26 subjects in control group and 28 subjects in the OC group.
Discussion
The study was conducted on a selected population of young women in whom the main factors affecting variability of bone remodeling markers were excluded [26], [27], [28], [29], [30], [31] and variability in urinary PYR and D-PYR measurements was minimized and standardized by applying the recommendations of Vesper et al. [30]. It can be assumed that the bone markers evaluated here provide a dynamic picture of the bone turnover rate [35] in a population of young postadolescent women.
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Acknowledgements
The authors thank Franca Fadda and Kate Jenkins for typing and revising the manuscript, and midwives Amalia Loi and Francesca Melis for their work with study participants.
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