Pearce Karma, Gleeson Kaori, Tremellen Kelton
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
Hum Reprod. 2015 Sep;30(9):2171-7. doi: 10.1093/humrep/dev167. Epub 2015 Jul 22.
Is there a relationship between serum anti-Mullerian hormone (AMH) levels and seasonal variations in serum vitamin D in ovulatory and polycystic ovary syndrome (PCOS) women?
Serum AMH levels were not associated with serum vitamin D status even after controlling for relevant co-variants, with this finding being consistent for all causes of infertility. As expected, seasonal variations in serum vitamin D were observed between summer and winter.
AMH plays an important role in maintaining ovarian reserve and modifying follicle sensitivity to FSH stimulation. Studies suggest that vitamin D has the ability to modify AMH production in vitro, yet only one clinical study reports the influence of vitamin D on AMH levels.
STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study analyzing the potential interaction of AMH and vitamin D for 340 women (58 PCOS and 282 ovulatory women) aged less than 40 years collected as part of their routine fertility assessment between January and December 2013 at a private fertility clinic in Adelaide, South Australia.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patient data including age, BMI, cause of infertility, antral follicle counts (AFC), serum AMH and vitamin D levels, smoking status, and menstrual cycle length for women aged less than 40 years of age, with serum AMH and vitamin D sampled within the same 4-week period were retrieved from a database. The hours of sunlight per day and daily UV index were extracted from a database at the South Australian Bureau of Meteorology, South Australia. Serum vitamin D (25-hydroxyvitamin D) levels were analyzed against seasonal variation in sunlight and UV exposure and serum AMH levels, while controlling for relevant co-variants.
Seasonal variations in serum vitamin D were observed between summer and winter (30% variance; P < 0.001), while serum AMH levels (mean ± SEM) remained unaffected by season status (36.9 ± 3.3 versus 38.5 ± 2.7 pmol/l; P > 0.05), even after controlling for relevant co-variants. Overall, no correlation was observed between serum AMH and vitamin D levels, in either the PCOS or ovulatory cohort. Serum vitamin D levels were not significantly related to the underlying cause of infertility (PCOS, diminished ovarian reserve, 'fertile' ovulatory controls).
LIMITATIONS, REASONS FOR CAUTION: The data used to generate the study findings are cross sectional in nature. While we acknowledge that a longitudinal study monitoring the relationship between serum AMH and vitamin D in individuals over the four seasons would have been ideal, we believe the current findings are robust as our four seasonal groups did not differ for any significant co-variant for serum AMH or vitamin D (age, BMI, PCOS status or AFC) and that there is no significant association between serum vitamin D concentration and AMH production.
At present, while in vitro studies suggest vitamin D has the potential to modify AMH production, clinical study findings are conflicting. If vitamin D does influence AMH production, this could have important therapeutic implications.
STUDY FUNDING/COMPETING INTERESTS: K.G. was supported through a University of South Australia summer scholarship. The authors have no competing interests.
排卵型及多囊卵巢综合征(PCOS)女性血清抗苗勒管激素(AMH)水平与血清维生素D的季节变化之间是否存在关联?
即使在控制了相关协变量之后,血清AMH水平仍与血清维生素D状态无关,这一发现对于所有不孕原因均一致。正如预期的那样,观察到夏季和冬季之间血清维生素D存在季节变化。
AMH在维持卵巢储备以及改变卵泡对促卵泡激素(FSH)刺激的敏感性方面发挥重要作用。研究表明,维生素D在体外具有改变AMH产生的能力,但仅有一项临床研究报告了维生素D对AMH水平的影响。
研究设计、规模、持续时间:这是一项回顾性队列研究,分析了2013年1月至12月在南澳大利亚阿德莱德一家私立生育诊所进行常规生育评估时收集的340名年龄小于40岁的女性(58名PCOS患者和282名排卵型女性)的AMH和维生素D的潜在相互作用。
参与者/材料、环境、方法:从数据库中检索患者数据,包括年龄、体重指数(BMI)、不孕原因、窦卵泡计数(AFC)、血清AMH和维生素D水平、吸烟状况以及年龄小于40岁且血清AMH和维生素D在同一4周内采样的女性的月经周期长度。每天的日照小时数和每日紫外线指数从南澳大利亚气象局的数据库中提取。在控制相关协变量的同时,分析血清维生素D(25-羟基维生素D)水平与日照和紫外线暴露的季节变化以及血清AMH水平之间的关系。
观察到夏季和冬季之间血清维生素D存在季节变化(方差为30%;P<0.001),而血清AMH水平(均值±标准误)不受季节状态影响(36.9±3.3对38.5±2.7pmol/L;P>0.05),即使在控制了相关协变量之后也是如此。总体而言,在PCOS队列或排卵型队列中,均未观察到血清AMH与维生素D水平之间存在相关性。血清维生素D水平与不孕的潜在原因(PCOS、卵巢储备功能减退、“可育”排卵对照)无显著相关性。
局限性、谨慎原因:用于生成研究结果的数据本质上是横断面数据。虽然我们承认,对个体在四个季节中血清AMH和维生素D之间的关系进行纵向研究将是理想的,但我们认为当前的研究结果是可靠的,因为我们的四个季节组在血清AMH或维生素D的任何显著协变量(年龄、BMI、PCOS状态或AFC)方面没有差异,并且血清维生素D浓度与AMH产生之间没有显著关联。
目前,虽然体外研究表明维生素D有可能改变AMH的产生,但临床研究结果相互矛盾。如果维生素D确实影响AMH的产生,这可能具有重要的治疗意义。
研究资金/利益冲突:K.G.获得了南澳大利亚大学的夏季奖学金支持。作者没有利益冲突。