The endocrine transition around menopause--a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women.

OBJECTIVE: The purpose of this study was to investigate the hormonal changes during the menopausal transition in a non-clinical population. METHODS: Fifty-nine healthy Norwegian women participated in a five year prospective longitudinal study during the transition from pre- to post-menopause, starting one to four years before menopause, and ending one to four years postmenopausal. None of these women were given hormone replacement therapy (HRT). Blood samples were collected every 12 months and luteinizing hormone (LH), follicle stimulating hormone (FSH), steroid hormone binding globuline (SHBG), prolactin (PRL), estradiol (E2), estrone (E1), testosterone, androstendione, dehydroepiandrostendione-sulphate (DHEA-S), and thyroid stimulating hormone (TSH) were analyzed. RESULTS: The serum levels of FSH and LH, E2 and E1 profile essentially confirmed previous data obtained in cross-sectional studies. A continuous increase in serum FSH and LH and a concomitant fall in E2 and E1 were observed in all women before menopause and in the two postmenopausal years. Both androstendione and testosterone showed a decline three years before menopause. After the menopause, however, there were fluctuations in the testosterone levels. Androstendione correlated positively with both E2 and E1 and testosterone postmenopausally. Body mass index (BMI) did correlate with testosterone, but not with androstendione. BMI correlated negatively with SHBG. No correlation was found between BMI and E2, E1, FSH and LH. CONCLUSION: This longitudinal prospective study of hormonal changes during the transition from pre- to postmenopause indicates that not only estrogen hormonal changes, but androgen hormonal changes as well, precedes the menopause by several years.     

Reproductive hormones: ageing and the perimenopause

This review explores the pituitary-ovarian hormones involved with ageing and the onset of menopause. The serum patterns of pituitary-ovarian hormones throughout the menstrual cycle alter as menopause approaches. The increase in follicular phase FSH prior to menopause is attributed to an early decline in the ovarian hormone, inhibin B, which negatively regulates follicle-stimulating hormone (FSH) secretion. Serum inhibin B is believed to reflect the age-related decrease in ovarian follicle reserve, which is the primary source of serum inhibin B. The later rise in serum luteinizing hormone (LH) during the menopause transition is due to a cessation of ovarian follicle development. Hormonal patterns during the luteal phase of the menstrual cycle also show changes with age but these changes are poorly understood.     

Follicular phase hormone levels and menstrual bleeding status in the approach to menopause

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.     

Inhibin B and ovarian function after total abdominal hysterectomy in women of reproductive age.

The aim of this prospective study was to assess ovarian function using clinical and endocrine parameters in women of reproductive age who underwent total abdominal hysterectomy. Sixty-one women, aged 40 mIU/ml, estradiol of < 20 pg/ml and inhibin B of < 5 ng/ml, compatible with ovarian failure. In the control group, all the parameters studied remained unchanged. These results suggest that total abdominal hysterectomy accelerates the decline in ovarian function in women of reproductive age.     

Inhibins, activins, and follistatin in the aging female and male

Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current conceptual roles in aging.     

Inhibin-producing ovarian granulosa cell tumor as a cause of secondary amenorrhea: case report and review of the literature

We report the case of 31-year-old patient with an inhibin B-secreting granulosa cell tumor of the left ovary who presented with secondary amenorrhea. Preoperative serum hormonal levels were as follows: follicle-stimulating hormone (FSH) 0.3 mIU/mL, luteinizing hormone (LH) 9.81 mIU/mL, estradiol 142.0 pg/mL and inhibin B 2429 pg/mL. Gonadotropin-releasing hormone (GnRH) test revealed no FSH response and a normal LH response. After removal of the tumor, the levels of FSH and inhibin B returned to within the normal range, and regular menses resumed 27 days postoperatively. In premenopausal women, secondary amenorrhea may be the initial manifestation of granulosa cell tumor. A low FSH level coupled with normal levels of E2 and LH, the inhibition of the FSH response to GnRH and an elevated inhibin level suggest the presence of an inhibin-secreting ovarian tumor and also rule out the possibility of isolated FSH deficiency.     

Initial analysis of variability among basal hormone biomarkers of ovarian reserve

The most commonly used biomarker tests of ovarian reserve are basal hormone measurements during the early follicular phase, including mainly FSH but also oestradiol, FSH:LH ratio, and inhibin B. This study was designed to assess prospectively the intra- and inter-cycle variability of serum values of those hormone biomarkers in the early follicular phase of consecutive cycles in a group of women candidates for assisted reproduction. Fifty eumenorrhoeic women underwent blood sampling for hormone measurement on cycle day 3 for three consecutive cycles, and during the first study cycle, daily samples were obtained on cycle days 2, 3, 4 and 5. No significant difference was detected among FSH concentrations and FSH:LH ratios during cycle days 2-5; in contrast, oestradiol and inhibin B were not constant through the early follicular phase. No difference in FSH or inhibin B serum concentrations and FSH:LH ratio on cycle day 3 during three consecutive cycles was noted; however, significant inter-cycle variability for oestradiol serum concentration on cycle day 3 was detected. FSH and inhibin serum concentrations, and FSH:LH ratio varied significantly less than oestradiol on cycle day 3, but inter-cycle variability was similar for the first three hormonal biomarkers of ovarian reserve. There was significantly less intra-cycle variability of FSH serum concentration and FSH:LH ratio than oestradiol and inhibin B serum concentrations. Basal FSH serum concentrations (or FSH:LH ratio) during the early follicular phase showed neither significant inter-cycle nor intra-cycle variability when measured during 3 consecutive months in an assisted reproduction patient population, thus offering greater flexibility of pretreatment sampling.     

Does obesity compromise ovarian reserve markers? A clinician’s perspective

Objective

The aim of the study was to ascertain if increasing body mass index (BMI) adversely affects ovarian reserve among infertile women of Asian origin undergoing in vitro fertilization (IVF).

Materials and methods

This prospective study on 183 women was carried out in the infertility clinic of All India Institute of Medical Sciences, New Delhi, India. Blood hormonal assay in all patients including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B was performed on day 2/3 of a spontaneous cycle. A transvaginal ultrasonographic examination on day 2–5 of the menstrual cycle was done for antral follicle count (AFC) and ovarian volume. A correlation between BMI and ovarian reserve parameters like FSH, LH, inhibin B, antral follicle count and ovarian volume was noted.

Results

Age was comparable in the three BMI groups. The mean duration of infertility was 8.38 years. Compared to the normal weight, the overweight and obese women had a statistically significantly low inhibin B (p < 0.0259). The AFC when taken together on both sides was not statistically significant between the groups; however, the overweight and obese women had a significantly low AFC (p < 0.0129) on the right side.

Conclusion

Incorporating anti-mullerian hormone, a newer marker for ovarian reserve, may benefit these obese infertile women. Further work is required to elucidate the mechanisms underlying the effect of obesity on inhibin B as a marker of ovarian reserve in infertile women. The best marker to check the ovarian reserve is perhaps the woman’s performance during an IVF cycle. However, considering the psychological and financial stress of the procedure, it may seem wise to consider counseling of obese women on their expected performance in the first cycle of IVF through such studies.     

年龄与卵巢功能——对卵巢衰老的认识

女性生育力高峰出现在20~30岁的中、晚阶段,此后生育力逐渐降低直到绝经。生育力下降发生在FSH水平上升,抑制素B下降和月经周期长度改变之前。抗苗勒管激素是较抑制素B出现更早的标志物。窦卵泡数的变化和月经周期长度可变性增强反映生殖衰老加速。生殖衰老过程,在人群存在一个普遍适用的规律;但每个个体的衰老进程是她所受多种复杂因素相互作用的结果。     

Differential effects of aging on activin A and its binding protein, follistatin, across the menopause transition

To assess the involvement of ovarian-derived regulatory proteins in FSH modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin (FS) in 79 women from the following five groups: young cycling, older cycling, perimenopause (PERI), spontaneous menopause (PM), and surgical menopause receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian function, no group differences were observed in activin A, barring a tendency for an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups and negatively correlated with advancing age.     

Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging

OBJECTIVE: To investigate whether follicular phase characteristics associated with ovarian aging can be observed in women of normal reproductive age, who had previously shown a poor response to ovarian hyperstimulation for IVF. DESIGN: Observational, prospective study. SETTING: Tertiary fertility center. PATIENT(S): Eleven regularly cycling, ovulatory women, aged 29-40 years who previously presented with fewer than four dominant follicles after ovarian hyperstimulation for IVF. INTERVENTION(S): Frequent serum hormone assessments and transvaginal ultrasound during the follicular phase of a spontaneous, unstimulated cycle. MAIN OUTCOME MEASURE(S): Duration of the follicular phase; serum LH, FSH, E(2), P, inhibin A, and inhibin B levels; and number of antral follicles observed by ultrasound. Results were compared with the cycle characteristics of a reference population of 38 healthy normo-ovulatory women aged 20-36 years (as published elsewhere). RESULT(S): Poor responders had significantly fewer antral follicles than controls. Median FSH concentrations were significantly higher compared with controls, but the majority had FSH levels within the normal range. Follicular phase P levels were significantly higher in poor responders. Duration of the follicular phase, E(2), and inhibin A and inhibin B serum levels did not differ between poor responders and controls. CONCLUSION(S): Normo-ovulatory regularly cycling women with a previous poor response to ovarian hyperstimulation for IVF show follicular phase characteristics suggestive of ovarian aging.     

Comparison of Basal and Clomiphene Citrate Induced FSH and Inhibin B, Ovarian Volume and Antral Follicle Counts as Ovarian Reserve Tests and Predictors of Poor Ovarian Response in IVF

PURPOSE: To compare basal and clomiphene citrate (CC) induced follicle-stimulating hormone (FSH), estradiol (E2), and inhibin B levels with ultrasound indices of ovarian reserve in infertile women and to test the prognostic value of these tests on response to ovarian stimulation in in vitro fertilization (IVF). METHODS: Fifty-six patients had basal and CC induced serum hormone levels and ultrasound measured mean ovarian volume (MOV) and mean antral follicle counts (MFC). Thirty-two patients were then appropriately selected to have a total of 41 cycles of IVF/ICSI treatment. RESULTS: Women with diminished ovarian reserve had lower MOV, MFC, day 3 and day 10 inhibin B levels (p < 0.001). Only basal and CC induced FSH and inhibin B correlated with MOV and MFC. Poor responders in IVF/ICSI had higher basal FSH (p < 0.05), lower basal and induced inhibin B levels (p < 0.05), and lower MOV and MFC (p < 0.01) than normal responders. Ovarian volume alone was better than age and basal hormones in predicting poor ovarian response, while abnormal CC test was the only independent significant factor in predicting ovarian response. However, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: CC test and ovarian volume are better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles.     

The role of inhibin in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its severest manifestations, is associated with anovulation, hyperandrogenism and metabolic imbalance. The biochemical markers for the condition can include a significantly raised LH:FSH ratio and a raised testosterone concentration, indicating a derangement of the hypothalamo--pituitary--ovarian axis which may be primary or secondary to a primary ovarian pathology. The bioactive inhibins are heterodimeric glycoproteins consisting of alpha-betaA (inhibin A) and alpha-betaB (inhibin B) subunits. They play an endocrine role in co-regulating (with oestradiol) the suppression of FSH during the late follicular and luteal phases of the ovarian cycle and they are implicated in intraovarian paracrine signalling. Inhibin B, which is the predominant form in small pre-ovulatory follicles, increases in concentration from early in the follicular phase to reach a peak coincident with the onset of the decrease in FSH which forms the basis of the pattern of mono-ovulation seen in normo-ovulatory women. Several unique features of the dysovulation of women with PCOS, namely their failure to recruit and develop a dominant follicle despite having 'normal' concentrations of endogenous FHS, the raised LH:FSH ratio and their exquisite sensitivity to exogenous FSH injections, may be explained by their significantly higher inhibin B concentrations. Studies into inhibin B parameters in women with PCOS demonstrate that women with anovular PCOS have significantly higher concentrations of circulating inhibin B and that they lack the pulsatile pattern of secretion that can be detected in normo-ovulatory women during the mid-follicular phase. The inhibin B response to ovulation induction with clomiphene citrate in women with PCOS differs from that in normo-ovulatory women taking the antioestrogen. Women with PCOS who over-respond to ovulation induction with injected FSH in a 'low-dose' step-up protocol' and recruit multiple follicles have significantly higher concentrations of pre-treatment inhibin B than PCOS subjects who do not.     

Gonadotropins and prolactin serum levels during the perimenopausal period: correlation with diverse factors

We studied 490 women aged 35 to 55 years randomly selected from the urban population of León, México. The mean age for the onset of menopause, calculated with a probit regression was 48.5 years. The median of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased with the rate of menopause women, but the 10th percentile for both hormones did not increase above 15 IU/L in older groups. Meanwhile, prolactin did not change. In menopause women FSH correlated positively with cigarette smoking, and negatively with body mass index. Luteinizing hormone had negative correlation with the number of pregnancies. Most symptoms studied were not associated with menopause or gonadotropins levels, except hot flushes, and the empty nest syndrome. It was concluded that during menopause, FSH increases with the smoking habit, and decreases with overweight.     

The role of inhibin in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its severest manifestations, is associated with anovulation, hyperandrogenism and metabolic imbalance. The biochemical markers for the condition can include a significantly raised LH:FSH ratio and a raised testosterone concentration, indicating a derangement of the hypothalamo-pituitary-ovarian axis which may be primary or secondary to a primary ovarian pathology. The bioactive inhibins are heterodimeric glycoproteins consisting of α-βA (inhibin A) and α-βB (inhibin B) subunits. They play an endocrine role in co-regulating (with oestradiol) the suppression of FSH during the late follicular and luteal phases of the ovarian cycle and they are implicated in intraovarian paracrine signalling. Inhibin B, which is the predominant form in small pre-ovulatory follicles, increases in concentration from early in the follicular phase to reach a peak coincident with the onset of the decrease in FSH which forms the basis of the pattern of mono-ovulation seen in normoovulatory women. Several unique features of the dysovulation of women with PCOS, namely their failure to recruit and develop a dominant follicle despite having ‘normal’ concentrations of endogenous FHS, the raised LH:FSH ratio and their exquisite sensitivity to exogenous FSH injections, may be explained by their significantly higher inhibin B concentrations. Studies into inhibin B parameters in women with PCOS demonstrate that women with anovular PCOS have significantly higher concentrations of circulating inhibin B and that they lack the pulsatile pattern of secretion that can be detected in normo-ovulatory women during the mid-follicular phase. The inhibin B response to ovulation induction with clomiphene citrate in women with PCOS differs from that in normo-ovulatory women taking the anti-oestrogen. Women with PCOS who over-respond to ovulation induction with injected FSH in a ‘low-dose’ step-up protocol’ and recruit multiple follicles have significantly higher concentrations of pre-treatment inhibin B than PCOS subjects who do not.     

Side of ovulation and its effects on uterine and ovarian stromal blood flow and reproductive hormones

OBJECTIVE: Effect of the side of ovulation on uterine, ovarian, and follicular blood flow parameters and various hormone levels. DESIGN: Prospective, observational study. SETTING: Fertility Clinic, St. George's Hospital. PATIENT(S): Nineteen women with regular menstrual cycles. Pulsed Doppler measurements and serum hormonal concentrations during midfollicular, periovulatory, and midluteal phase for three successive cycles. MAIN OUTCOME MEASURE(S): Doppler blood flow and serum hormones. RESULT(S): Doppler blood flow of the ovarian stroma and follicular and uterine arteries showed no differences in the three phases between the right and left sides. Left-side uterine peak systolic velocity (PSV) (right-side PSV, 31.51cm/s; left-side PSV, 37.38 cm/s) during the periovulatory phase tended to be higher in the nondominant ovary; however, this was not quite significant. The serum hormone concentration showed no significant differences. CONCLUSION(S): The side of ovulation did not influence the Doppler blood flow to the ovarian stroma or follicular and uterine arteries. The side of ovulation had no effect on serum FSH, LH, 17beta-estradiol, P, inhibin A, or inhibin B levels.     

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.     

Concentrations of inhibins and activin in women undergoing stimulation with recombinant follicle-stimulating hormone for in vitro fertilization treatment

OBJECTIVE: To investigate the influence of human recombinant follicle-stimulating hormone (FSH) on circulating serum concentrations of the ovarian proteohormones inhibin A, inhibin B, pro alpha-C, and activin A and serum levels of estradiol after down-regulation with GnRH analogue. DESIGN: Serum concentrations of ovarian proteohormones and estradiol. SETTING: Academic clinical practice. PATIENT(S): 30 women who underwent assisted reproductive techniques. INTERVENTION(S): Blood samples were analyzed for inhibin A, inhibin B, pro alpha-C, activin A, and estradiol during IVF treatment at points coinciding with pituitary down-regulation, stimulation with recombinant FSH, ovulatory triggering, and the luteal phase of the cycle. RESULT(S): Activin A levels did not change with recombinant FSH stimulation. In women with a sonographically detected leading follicle >17 mm in diameter, levels of inhibin A, pro alpha-C, and estradiol increased significantly (P<.05). The increase in inhibin B level was not statistically significant. In patients without adequate follicle development during FSH stimulation, serum levels of inhibins remained low and did not significantly deviate from values measured before stimulation. CONCLUSION(S): Inhibin A and pro alpha-C are effective markers of follicular development and may be effective additions to estradiol as a marker.     

Serum inhibin A, inhibin B, and pro-alphaC levels are altered after surgically or pharmacologically induced menopause

OBJECTIVE: To evaluate the course of changes in serum inhibin A, inhibin B, and pro-alphaC levels in women with surgically or pharmacologically induced menopause. DESIGN: Longitudinal study. SETTING: Academic Health Center of Siena, Siena, Italy. PATIENT(S): Four groups of women were studied: [1] surgical menopause including bilateral oophorectomy (n = 15), [2] amenorrhea induced by GnRH-analogue for treatment of endometriosis (n = 13), [3] amenorrhea induced by antineoplastic chemotherapy before (n = 15) and after chemotherapy (n = 13), and [4] control physiological menopause (n = 67). INTERVENTION(S): Collection of blood specimens. MAIN OUTCOME MEASURE(S): Serum inhibin A, inhibin B, and pro-alphaC concentrations were measured by using specific two-site ELISAs. RESULT(S): Following oophorectomy, serum inhibin A, inhibin B, and pro-alphaC levels were decreased on the first postoperative day; on the fifth postoperative day they were still significantly reduced. Women with amenorrhea induced by GnRH-analogue treatment exhibited serum inhibin A and pro-alphaC levels that were significantly higher than those observed in physiological menopause. Patients undergoing antineoplastic chemotherapy had higher serum inhibin A levels than those in physiological menopause, whereas inhibin B and pro-alphaC levels did not differ. During the course of chemotherapy, median serum inhibin A concentrations were similar to those of patients evaluated after the suspension of treatment. In postmenopause, inhibin A, and inhibin B levels were low, whereas levels of pro-alphaC were still detectable. CONCLUSION(S): Circulating levels of inhibin A, inhibin B, and pro-alphaC are reduced after oophorectomy. Women with amenorrhea induced by GnRH-analogue treatment or by antineoplastic chemotherapy still produce inhibin A and pro-alphaC. This probably reflects a residual ovarian function and hormone synthesis. Therefore, the ovary may be a source of pro-alphaC after menopause; significant amounts of pro-alphaC are present in circulation after natural menopause, but not after oophorectomy.     

Heterozygosity for the classical galactosemia mutation does not affect ovarian reserve and menopausal age

Female patients with classical galactosemia (galactose-1-phosphate uridyltransferase [GALT] deficiency) frequently suffer from premature ovarian failure, despite treatment with a galactose-restricted diet. Earlier research has suggested an association between heterozygosity for GALT mutations and early menopause. This study evaluates the effect of carriership for classical galactosemia on ovarian reserve and menopausal age. Proven female carriers of classical galactosemia were recruited via the Dutch Galactosemia Society. All 58 participants underwent a structured interview regarding fertility, smoking status, and menopause. To determine ovarian reserve, 42 premenopausal GALT carriers underwent ovarian antral follicle count (AFC) by transvaginal ultrasound and early follicular phase blood sampling for hormonal measurement of follicle-stimulating hormone (FSH), inhibin B, and anti-Müllerian hormone (AMH). These ovarian reserve parameters were compared with a cohort of proven fertile women (n = 166). The mean age at menopause in GALT carriers was 49.7 years, which is not different from the mean age at menopause in the general population in the Netherlands. There was no difference in FSH, inhibin B, and AMH levels or in the AFC (when corrected for age and smoking status) between 42 premenopausal GALT carriers and controls. The authors conclude that there is no evidence that GALT mutation carriership affects ovarian reserve or menopausal age.