Decline In anti-Müllerian Hormone Levels Research Articles

Anti-Müllerian Hormone Level Decline in Patients Undergoing Hysterectomy With and Without Oophorectomy Compared With Natural Menopause.

To evaluate the relationship between hysterectomy with and without ovarian conservation and the onset of ovarian failure using anti-müllerian hormone (AMH) levels and imputed final menstrual period (FMP). A total of 1,428 women with an observed FMP and 232 women who underwent hysterectomy (159 with bilateral salpingo-oophorectomy [BSO], 13 with one ovary conserved, and 60 with both ovaries conserved) and who had serial AMH measurements were included from SWAN (The Study of Women's Health Across the Nation), a multi-ethnic, multi-site, community-based study. Anti-müllerian hormone levels were sampled annually with at least one presurgery or pre-FMP measurement at least one postsurgery or post-FMP measurement. Surgery-related differences in patterns of AMH levels with respect to surgery date or FMP were estimated using piecewise linear mixed modeling; differences in age at first undetectable AMH level were estimated using survival analyses. Patients with conservation of one or both ovaries or natural menopause demonstrated similar patterns of decline in AMH levels when anchored to surgery or FMP. Patients with hysterectomy (all types) had a later counterfactual FMP (52.9±0.2 SEM) compared with the observed FMP in those with natural menopause (52.1±0.1 years, P =.002). Those undergoing BSO had an immediate reduction in AMH level to undetectable after surgery. Hysterectomy does not lead to a more rapid decline in AMH levels postoperatively compared with natural menopause. Patients undergoing BSO have a rapid loss of AMH, consistent with complete removal of the ovaries. These data suggest that hysterectomy as currently performed does not compromise ovarian reserve.

Initial Preoperative Hemoglobin Level Affects the Rate of Decline in Anti-Müllerian Hormone Levels after Laparoscopic Ovarian Cystectomy in Women with Ovarian Endometriosis.

To determine the factors affecting the decline in ovarian reserve following laparoscopic ovarian cystectomy (LOC) in women with ovarian endometriosis. This retrospective study included 22 women, aged 25-45 years, with regular menstrual cycles who underwent unilateral LOC and were diagnosed with ovarian endometriosis at a university hospital. Blood samples were collected preoperatively and on the third postoperative day to determine the serum anti-Müllerian hormone (AMH) levels for assessment of the decline in ovarian reserve during the early postoperative period. The preoperative hemoglobin level, white blood cell count, and AMH level were associated with changes in the AMH level after unilateral LOC. Among these parameters, only the preoperative hemoglobin level was correlated with the rate of decline in postoperative AMH levels. The preoperative serum AMH level was correlated with the amount of postoperative AMH change but not with its rate of decline. Preoperative hemoglobin levels may be associated with the rate of decline in AMH levels in the early postoperative period after unilateral LOC.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Association of Myomectomy With Anti-Müllerian Hormone Levels and Ovarian Reserve.

To assess whether open and minimally invasive myomectomy are associated with changes in postoperative ovarian reserve as measured by serum anti-müllerian hormone (AMH) level. This prospective cohort study included patients who were undergoing open abdominal myomectomy that used a tourniquet or minimally invasive (robot-assisted or laparoscopic) myomectomy that used vasopressin. Serum AMH levels were collected before the procedure and at 2 weeks, 3 months, and 6 months after surgery. The mean change in AMH level at each postsurgery timepoint was compared with baseline. The effect of surgical route on the change in AMH level at each timepoint was assessed by using multivariable linear regression. A subanalysis evaluated postoperative changes in AMH levels among the open myomectomy and minimally invasive myomectomy groups individually. The study included 111 patients (mean age 37.9±4.7 years), of whom 65 underwent open myomectomy and 46 underwent minimally invasive myomectomy. Eighty-seven patients contributed follow-up data. Serum AMH levels declined significantly at 2 weeks postsurgery (mean change -0.30 ng/mL, 95% CI -0.48 to -0.120 ng/mL, P=.002). No difference was observed at 3 months or 6 months postsurgery. On multiple linear regression, open myomectomy was significantly associated with a decline in AMH level at 2 weeks postsurgery (open myomectomy vs minimally invasive myomectomy: β=-0.63±0.22 ng/mL, P=.007) but not at 3 months or 6 months. Subanalysis revealed a significant decline in mean serum AMH levels in the open myomectomy group at 2 weeks (mean change -0.46 ng/mL, 95% CI -0.69 to -0.25 ng/mL, P<.001) postsurgery but not at three or 6 months. In the minimally invasive myomectomy group, no significant differences in mean AMH levels were detected between baseline and any postoperative timepoint. Myomectomy is associated with a transient decline in AMH levels in the immediate postoperative period, particularly after open surgery in which a tourniquet is used. Anti-müllerian hormone levels returned to baseline by 3 months after surgery, indicating that myomectomy is not associated with a long-term effect on ovarian reserve, even with the use of a tourniquet to decrease blood loss. This study was funded in part by a Roche Diagnostics Investigator-Initiated Study Grant.

Can Anti-Müllerian Hormone Be a Reliable Biomarker for Assessing Ovarian Function in Women Postchemotherapy?

PurposeThe predictive value of anti-Müllerian hormone (AMH) for ovarian dysfunction postchemotherapy is controversial. This study aimed to evaluate the value of serum AMH levels clinically and theoretically.Patients, Animals, and MethodsWe detected the serum estradiol, follicular stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels in 144 premenopausal women with breast cancer receiving cyclophosphamide-based chemotherapy. The hormone levels before and postchemotherapy were compared; the correlations among the hormones and amenorrhea and menstrual recovery were analyzed. In addition, the serum AMH levels were detected randomly in 177 normal healthy women and 36 normal female C57BL/6J mice of different ages; meanwhile, the status of ovarian follicles was also examined. Furthermore, 72 Balb/c nude mice with breast cancer were randomly assigned to three groups that received different doses of cyclophosphamide (CTX) (control, 100 mg/kg, and 200 mg/kg), and the alterations in serum AMH levels and ovarian follicles were recorded and analyzed.ResultsChemotherapy-induced amenorrhea was associated with prechemotherapy AMH levels, E2 levels, and FSH levels (P < 0.0001). The recovery of menstruation was associated with prechemotherapy AMH levels (P < 0.0001), but not with E2 and FSH levels (P > 0.05). In patients with breast cancer treated with chemotherapy, the serum AMH levels did not differ significantly between the pre- and post-chemotherapy periods in patients aged <35 years (P > 0.05), whereas a dramatic reduction was detected in patients aged >35 years (P < 0.0001). In healthy women, the serum AMH levels declined sharply after 35 years of age (P < 0.0001) and remained relatively stable at a younger age. Similar results were obtained in experiments using normal mice. The cancer-bearing mice exposed to 200 mg/kg CTX exhibited a significant decline in AMH levels and a remarkable decrease in the number of primordial and growing follicles (P < 0.0001).ConclusionOur results indicate that AMH is an efficient marker for predicting postchemotherapy ovarian function exclusively in premenopausal female patients with breast cancer aged >35 years.

Anti-Müllerian hormone levels before and after uterine artery embolization

Objective: To determine the effects of uterine artery embolization (UAE) on ovarian reserve as measured by Anti-Müllerian hormone (AMH) levels.Material and methods: Non-randomized, observational study of 89 women 23–40 years of age who received UAE. Control hormone levels were measured prior to UAE and the first post-embolization measurement was taken at various times post-procedure (mean = 190 ± 229 days).Results: Historical work verified by our earlier work has shown that AMH levels decline with age. Regression analysis allows us to determine whether UAE contributes to a greater decline in AMH values over that naturally occurring with aging. The effect of the procedure was found to contribute no deleterious effect to the natural decline in AMH levels. In addition, multiple blood draws were obtained from 32 patients up to 47 months post-UAE. Regression studies with these patients as their own controls showed no long-term diminishment of ovarian reserve due to the UAE procedure.Conclusions: Earlier reported data are consistent with larger sample size. UAE does not affect ovarian reserve in women <40 as evidenced by no significant change in AMH levels after embolization. Women who are of reproductive age and have uterine fibroids can consider UAE without concern for adverse effects on their fertility.

Anti-Müllerian hormone in type 2 and gestational diabetes during the second half of pregnancy: relationship with sexual steroid levels and metabolic parameters

Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation. A prospective study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were followed up during the second half of pregnancy. Clinical assessments and blood samples were collected at 26.7 (25–27.8); 34 (32–34.9) and 37.5 (37–40) weeks of gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD and C (p = .07). A decline of AMH levels during the second half of gestation was observed in the three groups (p < .0001). AMH levels were negatively associated with age (p < .001). A positive association between AMH and testosterone (p < .05) was found in all groups. A progressive decline of AMH levels is observed in diabetic and healthy women during the second half of pregnancy. Testosterone levels are an independent factor that influences AMH levels during pregnancy. However, AMH levels are not affected by the presence of diabetes during gestation.

Surgical excision of ovarian endometriomas: Does it truly impair ovarian reserve? Long term anti‐Müllerian hormone (AMH) changes after surgery

The long-term effects of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral ovarian endometriomas were evaluated. A total of 22 patients undergoing laparoscopic cystectomy for unilateral endometrioma (n = 10) and bilateral endometriomas (n = 12) were included in the study. Serum anti-Müllerian hormone (AMH) levels significantly decreased from the baseline value (3.98 ± 3.27 ng/mL) one (1.67 ± 1.56 ng/mL), three (2.01 ± 1.70 ng/mL), and six months (2.43 ± 2.39 ng/mL) postoperatively. There was no difference between preoperative and 12 month postoperative AMH levels (4.01 ± 3.39 ng/mL) (P > 0.05). Patients with bilateral endometriomas had a significantly higher rate of decline in AMH levels 12 months after surgery than patients with monolateral endometriomas (P = 0.035), but in both groups there was no difference in AMH levels at one and 12 months postoperatively (P > 0.05). AMH levels temporarily decreased after laparoscopic cystectomy for ovarian endometriomas, with complete recovery of preoperative AMH values at 12 months postoperatively. This pattern was equal in patients with bilateral and unilateral ovarian involvement. Patients with bilateral cysts have higher rates of decline of AMH levels compared to patients with unilateral affection.

Anti-Mullerian-hormone levels during pregnancy and postpartum

BackgroundThe number of unintentionally childless couples is increasing as more couples seek to conceive for the first time in the third or fourth decade of the woman’s life. Determination of ovarian reserve is an essential component of infertility assessment. The Anti-Müllerian-Hormone (AMH) seems to be the most reliable predictor of ovarian reserve. In this study we analyzed AMH in a cohort of pregnant women without fertility impairment to determine age-dependent decline and possible AMH fluctuations during pregnancy and postpartum.MethodsA total of 554 healthy women aged 16 to 47 years without history of infertility or previous surgery on the ovaries were enrolled in the study between 1995 and 2012. In 450 women, a single measurement of AMH was taken during pregnancy, allowing for cross sectional analysis of trimester- and age-related differences in AMH levels. For another 15 women longitudinal data on AMH levels for all trimesters was recorded. In addition, for 69 women AMH was measured at the time just before and after delivery, and for another 20 AMH was measured just before delivery and once on each of the first four days after delivery. We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. Non-parametric statistical tests were used to compare AMH levels between age groups, trimesters and postpartum.ResultsComparison between the trimesters revealed a significant difference in AMH values at each trimester (first trimester: 1.69 ng/ml (IQR 0.71–3.10), second trimester: 0.8 ng/ml (IQR 0.48–1.41), third trimester: 0.5 ng/ml (IQR 0.18–1.00)). AMH significantly dropped during the course of pregnancy and immediately after delivery, whereas an increase was observed over the first four days postpartum. Women, greater than or equal to 35 years, showed significant lower AMH levels than those <35 years across all trimesters.ConclusionsAMH levels decrease during pregnancy. The decline in AMH levels during pregnancy indicates ovarian suppression. AMH levels recover quickly after delivery. AMH levels assessed in pregnant women are not an accurate indicator of ovarian reserve, since AMH levels during pregnancy seem not to be independent of gestational age.

Anti-mullerian hormone as predictor for ovarian reserve is associated with age at menopause in Fragile X premutation carriers

OBJECTIVE: Carriers of a premutation (repeat length 59-200) in the Fragile X mental retardation (FMR1) gene are known to be at risk for primary ovarian insufficiency (FXPOI). We investigated whether FXPOI is due to low ovarian reserve and/or accelerated decline of ovarian reserve. In addition, we addressed the question whether the levels of anti-Müllerian hormone (AMH) can predict the age at which menopause occurred. DESIGN: Retrospective controlled cohort study. MATERIALS AND METHODS: We determined AMH and follicle stimulating hormone (FSH) levels in blood samples with a 10 year interval (T1 and T2) in 101 women from 46 families with Fragile X syndrome. The levels of premutation carriers (PC) were compared to those of women with a normal repeat length or a full mutation. At T2 40 women were postmenopausal, with time intervals between AMH sample and final menstrual period (FMP) ranging from a few months to 10 years. Statistical multilevel analyses were performed using linear mixed models correcting for age, taking within family and within subject correlations into account. RESULTS: Premutation carriers (n=41) had significantly lower AMH levels (median AMH at T1 for PCs 0.21 ng/ml versus 1.27 ng/ml for control group (n=60), p=0.001), but showed an equal decline in AMH levels (PCs -62.5% versus control group -74.8%) over 10 years (p=0.13). FSH levels were higher (median FSH at T1 for PCs 12.3 IU/l versus control group 8.8 IU/l), but were not elevated (>10 IU/l) until above 40 years of age. Within 7 years until FMP, AMH levels were low and ranged from undetectable (<0.10 ng/ml) to 0.38 ng/ml, while FSH levels ranged from normal (<10 IU/l) to postmenopausal height (>40 IU/l). CONCLUSIONS: Fragile X premutation carriers demonstrate a similar decline in ovarian reserve as women without a risk of diminished ovarian reserve. Therefore, FXPOI may be associated with a predisposition to lower ovarian reserve. AMH levels may serve as a predictor of time until menopause (p=0.048) and, thus, may be useful at an early age.

Anti-Müllerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1 diabetes mellitus

Serum anti-Müllerian hormone (AMH) levels decrease early during the transition to menopause and women with type 1 diabetes mellitus (DM1) experience menopause at a younger age. We hypothesized that older women with DM1 will have lower AMH levels than controls. We studied ovarian function in women with DM1 (n = 66) and healthy controls (n = 58), all <45 years old. Steroids, gonadotrophins, AMH and inhibin B levels were measured during the follicular phase. Piece-wise regression analysis demonstrated that AMH levels begin to decrease at 33 years of age in both groups. This age limit was used to compare data in both groups. AMH levels were lower in DM1 women than in controls >33 years (4.1 +/- 4.2 versus 9.5 +/- 7.9 pmol/l, mean +/- SD, P = 0.006). A higher proportion of women with DM1 showed AMH levels in the menopausal range compared with controls (16.7% versus 3.4%, respectively, P = 0.02). For all patients, those with DM1 exhibited lower inhibin B levels than controls (89.3 +/- 51.7 versus 113.2 +/- 76.0 ng/ml, P < 0.05). FSH and estradiol were similar in both groups. Regression analysis showed an earlier decline in AMH levels in women with DM1 than controls. Even after age adjustment, DM1 was a significant factor for the determination of inhibin B and AMH levels. Lower AMH levels in women with DM1 during the fourth decade of life suggest the presence of an earlier decline in the ovarian follicle pool in these women. Further studies are needed to evaluate the mechanism of this complication.