Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women
Clara E. Van Ommen, Anthony Y.Y. Hsieh , Arianne Y.K. Albert
Elana R. Kimmel , Hélène C F Côté, Evelyn J Maan, Jerilynn C Prior, Neora Pick, Melanie C M Murray, CIHR Team on Cellular Aging, HIV Comorbidities in Women, Children (CARMA-Endo; CIHR CTN 277)
Women's Health Research Institute Vancouver BC Canada
Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, University of British Columbia, Rm. G227 - 2211 Wesb...ROR
We sought to better understand factors associated with ovarian aging in women with HIV (WWH).
Design
HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV.
Methods
We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders.
Results
WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women.
Conclusions
Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.
anti-mullerian hormone HIV, ovarian aging HIV women, leukocyte telomere length ovarian reserve, ovarian reserve markers HIV, reproductive aging HIV infection, AMH diminished ovarian reserve, telomere length reproductive aging, HIV women ovarian function, late reproductive age HIV, biological aging ovarian reserve
PMID 36726239 36726239 DOI 10.1097/QAD.0000000000003481 10.1097/QAD.0000000000003481 Clara Van Ommen et al. 2023, Clara Van Ommen 2023
Cite this article
Van Ommen, C. E., Hsieh, A. Y. Y., Albert, A. Y., Kimmel, E. R., Cote, H. C. F., Maan, E. J., Prior, J. C., Pick, N., Murray, M. C. M., CIHR Team on Cellular Aging, HIV Comorbidities in Women, & Children (CARMA-Endo; CIHR CTN 277) (2023). Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women. AIDS (London, England), 37(5), 769-778. https://doi.org/10.1097/QAD.0000000000003481
Van Ommen CE, Hsieh AYY, Albert AY, Kimmel ER, Cote HCF, Maan EJ, et al. Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women. AIDS. 2023;37(5):769-778. doi:10.1097/QAD.0000000000003481
Van Ommen, C. E., et al. "Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women." AIDS (London, England), vol. 37, no. 5, 2023, pp. 769-778.
Huang Y et al., 2024·Front Endocrinol (Lausanne)·
Open Access
Premature ovarian insufficiency/failure (POI/POF) is a significant issue for women of reproductive age. Anti-Müllerian hormone (AMH) is a potential biomarker of ovarian reserve, but its clinical value in diagnosing and predicting POI/POF remains unclear. This study aimed to analyze the correlation between AMH and basal follicle-stimulating hormone (FSH) levels in women aged 18 to 40 and evaluate AMH's predictive value for POI/POF. A total of 21,143 participants aged 18-40 who visited the gynecology department or underwent physical examinations at the International Peace Maternity and Child Health Hospital in Shanghai, China, from July 2016 to June 2021 were enrolled. Demographic information and laboratory test results were collected, including age, FSH, AMH, E2 and test dates. Participants were grouped by FSH and AMH levels, and subgroup analyses were performed to investigate the relationship between these hormones and age. The AMH level associated with POI risk was evaluated using restricted cubic splines (RCS) and logistic regression. Clinical benefit was assessed by decision curve analysis (DCA). Participants with higher FSH levels had significantly lower median AMH levels and vice versa(p<0.001). At AMH ≥ 0.5 ng/mL, FSH levels were normal or slightly elevated with age. At AMH level below 0.5ng/ml,basal FSH increased significantly with age. At FSH <10 IU/L, AMH levels show a trend of rising and then decreasing with age, reaching a peak at approximately 25 years old and gradually decreasing with age. At FSH ≥10 IU/L, AMH levels show a gradual downward trend with age, and at FSH >40 IU/L, AMH levels remain very low to undetectable values. The RCS showed that the risk of POI/POF in the overall population sharply increased until serum AMH reached a low level (below 0.5ng/ml). DCA showed that a low AMH level had good clinical diagnostic utility in predicting POI/POF. Our analysis of a large dataset suggests that serum AMH levels are inversely correlated with FSH levels and that AMH is a good predictor of POI until it drops to a low level.
The reference range and potential value of inhibin B are still unclear and controversial. This study aimed to define the variation trend of inhibin B in healthy women with age and explore its value in the reflection of ovarian reserve. A total of 2524 healthy reproductive age women from eight medical institutes nationwide were recruited. The variation tendency of inhibin B with age was primarily established in the first group of 948 women and validated in another 605. We evaluated the relationship between inhibin B and classic ovarian reserve and function markers. The potency of inhibin B in predicting AFC <5-7 was also estimated and compared with FSH. The nomogram showed that serum levels of inhibin B rapidly decreased after the age of 40. Inhibin B was positively correlated with AMH (R = 0.57, P < 0.001), AFC (R = 0.34, P < 0.001) and testosterone (R = 0.10, P = 0.002), and negatively correlated with FSH (R = -0.41, P < 0.001) and LH (R = -0.20, P < 0.001) and FSH/LH (R=-0.18, P < 0.001), while no correlation was found with PRL. Unexpectedly, Inhibin B (AUC = 0.74, P < 0.001 for the establishment population; AUC = 0.78, P < 0.001 for the validation population) had a slightly higher value than FSH (AUC = 0.71, P < 0.001 for the establishment population; AUC = 0.72, P < 0.001 for the validation population) in diagnosing AFC <5-7. For healthy reproductive age women, the decline of inhibin B can reflect decreased ovarian reserve effectively, having a good consistency with AMH and AFC. More importantly, inhibin B had an advantage in predicting AFC <5-7 compared with FSH, which suggested the potential of inhibin B in predicting ovarian response.
Grynnerup AG et al., 2012·Acta obstetricia et gynecologica Scandinavica
Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, thereby mirroring the size of the resting primordial follicle pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women; thus, it has a potential ability to predict future reproductive lifespan. The most established role for AMH measurements is before in vitro fertilization is initiated, because AMH can be predictive of the ovarian response, namely poor and hyper-responses. However, recent research has also highlighted the use of AMH in a variety of ovarian pathological conditions, including polycystic ovary syndrome, granulosa cell tumors and premature ovarian failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more comparable. Nevertheless, widespread clinical application awaits an international standard for AMH, so that results using future assays can be reliably compared.
Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.