Page 115 - Fertility in Women with Rheumatoid Arthritis Vruchtbaarheid van vrouwen met reumatoïde artritis

The more rapid decline of serum AMH levels over time in women with established RA indicates that chronic inflammation compromises ovarian function. The latter may even decline faster than was currently found in women with RA since the participants in this study represented a more fertile selection, with also less smokers, than the original PARA cohort. Since the original PARA cohort was already a relative healthy cohort,20 the true difference between women with RA and the general population may be even larger.
The compromised ovarian function in RA may be a direct effect of cumulative inflammatory damage to the ovaries. Although we found no signi cant association
between disease activity and AMH levels in current or previous analyses, there is a
relation with ACPA-positivity, which represents patients with on average more active
disease, often requiring a more intensive treatment strategy.28 We have previously
reported signi cantly lower serum AMH levels in ACPA-positive patients,19 and in the
current study more ACPA-positive than ACPA-negative patients appeared to have AMH
levels below the 10th percentile. Furthermore, in the linear mixed model, the negative
association of ACPA-positivity with serum AMH levels was present, although non-
signi cant, which may have been due to the lower number of subjects in this study.
The present idea among rheumatologists is that ACPA positive RA may be a different
disease than ACPA negative RA. It is not clear whether the reduced ovarian function is
a result of this probably different disease mechanism, or of increased inflammatory
damage due to longer periods of high disease activity. However, the lower AMH levels
in patients who are ACPA-positive, t with the overall concept that ACPA-positive RA
is a more destructive disease with more extra-articular manifestations.28 7 Otherwise, there may be a genetic basis for the compromised ovarian function in RA.
In genome-wide association studies (GWAS), not only genes linked to DNA repair and genome maintenance have been related to age at menopause, but also genes linked to immune response seem to determine the timing of menopause.8 Whether RA and early menopause share a common genetic basis, may be the focus of future research.
Regarding generalizability, we should consider the recent changes in diagnosis and treatment of RA. Where patients from the PARA cohort were classi ed as having RA according to the 1987 ACR criteria,21 nowadays RA is often recognized and diagnosed at an earlier stage, when less damage has been done.29 Furthermore, new treatment guidelines have been developed over the last decade, focusing on early combination therapy in a treat-to-target regimen, and the addition of biological disease modifying antirheumatic drugs such as tumor necrosis factor (TNF) inhibitors for a tighter disease
AMH in RA – longitudinal
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