Associations of premenopausal AMH levels with lipids profile using MenoCheck (picoAMH)

Objective
To assess whether lower premenopausal AMH and greater declines in AMH levels over menopausal transition (MT) would be associated with adverse changes with lipid profiles.

Methods
Serum samples from 1423 women aged 42 to 52 years were collected and picoAMH and lipid including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), calculated low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (apoA-1), and apolipoprotein B (apoB) were measured.

Results
In unadjusted models, lower premenopausal AMH levels and greater declines in AMH over the MT were significantly associated with higher levels of lipids. [per 1 log unit decrease in premenopausal AMH: Cholesterol β(se): 2.76(0.38) , log Triglycerides: 0.01(0.01), LDL-C: 1.86(0.35), apoB: 1.45(0.31), HDL-C: 0.54(0.17), apoA-1: 0.83(0.30), P values <0.006; per 1 log unit decline in AMH over MT: Cholesterol β(se): 2.80(0.15) , log Triglycerides: 0.01(0.002), LDL-C: 2.12(0.13), apoB: 1.09(0.12), HDL-C: 0.46(0.05), apoA-1: 2.44(0.16), P values <0.0001]. These associations largely remained significant in final, multivariable models except for triglycerides

Conclusions
Women with less ovarian reserve as reflected by lower premenopausal AMH levels and greater declines in AMH over the MT had a worse lipid profile. Measuring AMH earlier in the MT could help identify premenopausal women at increased risk of later CVD.

Reference:
El Khoudary SR, Wang L, Brooks MM, Matthews KA, Thurston RC, Crawford S, Derby C, Jackson EA, Lee JS, Un-Yong Chae C, McConnell DS, Finkelstein J. Associations of Anti-Mullerian Hormone Premenopausal Levels and Their Changes over the Menopausal Transition with Lipids: The Study of Women′s Health Across the Nation (SWAN). Presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA

Predicting the onset of menopausal vasomotor symptoms with MenoCheck (picoAMH)

Objective
To assess whether AMH predicts the onset of frequent VMS symptoms and contributes to the information independent of other serum markers

Methods
Serum samples from 919 women (aged 42 to 52 years were collected and picoAMH, estradiol, FSH, were measured. VMS and menopausal status based on menstrual bleeding were measured annually.

Results
Of 919 participants, 297 had incident frequent VMS. AMH level was significantly negatively associated (p<.0001) with incident frequent VMS (HR 0.28, 95% CI 0.23 – 0.34). Similar statistical model fits for AMH, estradiol, FSH, and menopause status taken one at a time. Though, a slightly higher associations of VMS with FSH compared with the other three markers, AMH remained significantly associated (p<.001) with incident frequent VMS after adjusting for menopausal status (adjusted HR 0.29, 95% CI 0.22 – 0.39), for estradiol (adjusted HR 0.36, 95% CI 0.27 – 0.50), and for FSH (adjusted HR 0.55, 95% CI 0.42 – 0.71).

Conclusions
AMH is useful for predicting the incidence of VMS, particularly frequent VMS, independent of other key markers of menopause stage based on menstrual bleeding or other reproductive hormones.

Reference:
Crawford S, Finkelstein J, Gold E, Greendale G, Harlow S, Joffe H, Kalra B, Kumar A, Martin D, Merillat S, Morrison A, Sluss P, Thurston R, Avis N. Predicting Onset of Menopausal Vasomotor Symptoms with Anti-Mullerian Hormone in the Study of Women’s Health Across the Nation (SWAN) Presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA

The association between picoAMH levels and new-onset sleep disturbance in women during menopausal transition

Objective
To investigate 1) whether low concentrations of AMH predict the new-onset of sleep disturbance generally, and awakenings specifically, and 2) whether vasomotor symptoms (VMS) mediate an association between AMH and new-onset sleep disturbance or awakenings during the MT

Methods
1098 and 1166 participants in new-onset sleep disturbance and awakenings analyses, respectively were included in the study. Annual assessments of AMH levels, self-reported sleep disturbances and VMS were collected.

Results
519 (47%) women reported sleep disturbance and 493 (42%) reported awakenings during follow-up (mean 6.4 yrs). AMH was significantly negatively associated with new-onset of sleep disturbance (hazard ratio [HR] 0.90, 95% CI 0.82–0.998, p=0.047) and awakenings (HR 0.90, 95% CI 0.81–0.995, p=0.040) after adjusting for all covariates except VMS. VMS were significantly associated with AMH, new-onset of sleep disturbance and awakenings (all p<0.0001). After further adjustment for VMS, AMH was no longer associated with new-onset of sleep disturbance (HR 1.08, 95% CI 0.97–1.20, p=0.16) or awakenings (HR 1.07, 95% CI 0.96–1.09, p=0.25).

Conclusion
AMH predicts the development of sleep disturbance in general and awakenings, during the menopause transition, but this association is mediated by VMS, which appears to drive the association between declining AMH levels and new-onset sleep problems.

Reference:
Joffe H, Crawford S, Bromberger JT, Kalra B, Kumar A, Morrison A, Finkelstein J, Kravitz JM. Vasomotor Symptoms Mediate the Association Between Anti-Mullerian Hormone Levels and New-Onset Sleep Disturbance in Women during the Menopause Transition: Study of Women’s Health Across the Nation (SWAN). Presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA

Assessment of incidence of early natural menopause using MenoCheck (picoAMH)

Objective
To assess the risk of incident of early natural menopause in women aged 32–44 using picoAMH

Methods
Premenopausal blood samples were collected as part of prospective Nurses’ Health Study II cohort. Participants were followed for 12 years for early natural menopause. Early menopause cases (n = 327) were women reporting natural menopause between blood collection and age 45. Controls (n = 491) experienced menopause after age 45 and included 327 cases matched to controls on the basis of age at blood draw (±4 months).

Results
In multivariable conditional logistic regression models adjusting for matching factors, each 0.10 ng/ml decrease in AMH was associated with a 14% higher risk of early menopause (P < 0.001). The odds ratios for early menopause for women with AMH levels of 1.5, 1.0 and 0.5 ng/ml compared to 2.0 ng/ml were 2.6, 7.5 and 23 (all P < 0.001). Significant associations were observed irrespective of smoking status, adiposity, infertility history and menstrual cycle characteristics. Furthermore, models assessing the predictive ability of AMH showed high concordance, and C-statistics were high, ranging from 0.68 (age ≤35) to 0.93 (age 42).

Conclusion
This is the first prospective study to evaluate whether AMH levels are associated with early menopause. These findings support the utility of AMH as a clinical marker of early menopause in otherwise healthy women.

Reference:
Bertone-Johnson ER, Manson JE, Purdue-Smithe AC, Steiner AZ, Eliassen AH, Hankinson SE, Rosner BA, Whitcomb BW. Anti-Müllerian hormone levels and incidence of early natural menopause in a prospective study. Hum Reprod. 2018 Jun 1;33(6):1175-1182.

Utility of MenoCheck (picoAMH) for predicting the time to the final menstrual period

Objective
To predict the likelihood that a woman would have her final menstrual period (FMP) within a specified duration of time based on her AMH levels.

Methods
Serum samples 3302 women aged 42 to 52 years were collected and picoAMH levels were measured.

Results
Women whose AMH values were 5-10 pg/mL had a 50% chance of having their FMP within 11 +/- 2 months and a 75% chance of having their FMP within 24 +/- 3 months. Adding age to the model sharpened predictions across all AMH categories.

Conclusions
When very low, (< 10 pg/mL) AMH can help predict a woman’s chance of having her FMP in the next year with reasonable precision. Women with AMH levels > 20 pg/mL are unlikely to become postmenopausal in the next 2 years. AMH appears to be a reliable marker of ovarian aging that can help predict the FMP and may allow clinically useful predictions of other changes linked to the MT.

Reference:
Finkelstein JS, Lee H, Burnett-Bowie SAM, Santoro N, Yu EW, Joffe H, Morrison A, Kumar A, Greendale GA, Gold E, Harlow S, Lasley BL, Derby C, Randolph JF, Matthews KA, Kravitz HM, McConnell DS, Brooks MM, Martin D, Darakananda K, Hirsch SC, Sluss PM. Utility of Anti-Mullerian Hormone (AMH) for Predicting the Time to the Final Menstrual Period: The Study of Women’s Health Across the Nation (SWAN). Presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA