PapersVitamin D and calcium dysregulation in the polycystic ovarian syndrome
Introduction
In 1935, Stein and Leventhal reported the association of enlarged polycystic ovaries with amenorrhea, hirsutism, and obesity [1]. Polycystic ovarian syndrome (PCO) has since been recognized to be one of the most common female endocrine disorders, characterized by hyperandrogenic chronic anovulation with infertility, irregular menses, dysfunctional uterine bleeding, acanthosis nigricans, and hirsutism [2]. The precise pathophysiologic mechanisms resulting in these endocrinologic disturbances are not known. The most widely accepted theory proposes that PCO is a self-perpetuating cycle of hormonal events with increased intra-ovarian concentrations of androgens, resulting in polycystic ovaries, theca cell hyperplasia, and arrested follicular cell development [3], [4], [5].
Recent animal investigations have established a role of calcium in oocyte activation and maturation, resulting in the resumption and progression of follicular development [6]. Attention had originally centered on the significance of calcium during oocyte activation at fertilization by either sperm or the divalent ionophore A23187. Based on evidence that the calcium ionophore A23187 activated the eggs of vertebrates and marine invertebrates by mediating calcium fluxes, Steinhardt et al. [7] proposed, in 1974, that calcium may have a universal role in egg activation. Since then, the importance of calcium in the regulation of both meiotic and mitotic cell division cycles in mammalian and non-mammalian oocytes has been of considerable interest [8]. The role of calcium oscillations during fertilization in the activation of both the non-mammalian and mammalian oocyte has been firmly established. Its role in triggering meiotic resumption and oocyte maturation in invertebrates is clear. In contrast, the precise role of calcium in oocyte differentiation and maturation in mammals is not as clearly defined, although it is strongly suggested by numerous animal investigations [9]. In mammals, maturation of the immature oocyte and the activation and fertilization of the mature egg are two separate events. Both may be regulated by changes in intracellular calcium.
Because of the importance of calcium in both oocyte activation and maturation, it was hypothesized that abnormalities in calcium homeostasis may, in part, underlie the pathogenesis of PCO. Disordered calcium regulation could be responsible for the follicular arrest manifesting as the reproductive and menstrual disturbances characterizing, in part, the PCO syndrome. The present investigation was conducted as an exploratory and observational trial, and provides evidence for this hypothesis.
Section snippets
Experimental
Premenopausal women between the ages of 18 and 50 years were enrolled in this study. Women were included if they met the 1990 National Institute of Health Consensus criteria [10] of polycystic ovarian syndrome with chronic oligomenorrhea/anovulation and signs of androgen excess (hirsutism, acne, alopecia). The following were exclusion criteria: ovarian androgen secreting tumors, adrenal androgen secreting tumors, Cushing’s syndrome, hyperprolactinemia, primary hyperparathyroidism, malignancy,
Results
Thirteen premenopausal women with documented chronic anovulation and hyperandrogenism were evaluated. Ages ranged from 21 to 41 years (31.1 ± 7.9). The weight of the women varied from 55 to 102 kg, with a mean body mass index of 30.6 kg/m2 (Table 1). Eleven women were Hispanic and two were Caucasian. None had a history of consuming dietary supplements or vitamins. All had evidence of hirsutism, three had acne, and two had alopecia. Five women had evidence of acanthosis nigricans. Nine had
Discussion
Polycystic ovarian syndrome appears to be confined exclusively to Homo sapiens. A similar paradigm in the rest of the animal kingdom is unknown. Infertility and arrested follicular development, however, are not exclusively human traits. They have been extensively studied in invertebrates and vertebrates. In this observational study, our results support the hypothesis that abnormalities in calcium homeostasis may be responsible for the arrested follicular development and the menstrual
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