Give Us This Day our daily germs
Graham A.W. Rook and John L. Stanford
Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. This fails to
maintain the correct cytokine balance and fine-tune T-cell regulation, and may lead to increased incidences of allergies and autoimmune diseases. If humans continue to deprive their immune systems of the input to which evolution has adapted it, it may be
necessary to devise ways of replacing it artificially.
Sunday, June 04, 2006
Ovarian aging: Is there a "norm"?
Ovarian aging: Is there a "norm"? Norbert Gleicher, MD
Female fertility declines with advancing age, principally because of changes in ovarian function. Ovarian aging always has been assumed to be the main culprit, but experience with human egg donation confirms that female fertility can basically be prolonged almost indefinitely, as long as "young" eggs are used in assisted reproduction.1
The decline in human fertility is predictable and can be quantified. Indeed, various authors have demonstrated that the downturn in women's fertility is the consequence of an age-dependent reduction in the number of remaining follicles, which starts during embryogenesis and continues. The initial pool of primordial follicles—at 16 to 20 weeks of fetal life—is believed to encompass approximately 6 to 7 million oocytes. At birth, the female's ovaries contain only 2 million oocytes, and by menarche, about 300,000 remain.2 That number is more than sufficient, as only about 450 monofollicular ovulations are required during a reproductive life of approximately 30 years.
Yet the number of remaining follicles does appear to matter, because when the follicular count falls to about 25,000—as it does in a physiologically normal ovary at approximately age 37.5—the decline in follicular numbers accelerates.3 Various authors, therefore, have suggested that what determines when a woman will experience menopause is not her age but how quickly her follicular count drops to approximately 1,000, the quantity at which menopause usually occurs.4 On average, that happens at age 51, or about 13 years after a woman reaches the 25,000-follicle milestone. In other words, at about age 37.5, a woman's fertility begins to accelerate, and about 13 years later, menopause sets in.
Female fertility declines with advancing age, principally because of changes in ovarian function. Ovarian aging always has been assumed to be the main culprit, but experience with human egg donation confirms that female fertility can basically be prolonged almost indefinitely, as long as "young" eggs are used in assisted reproduction.1
The decline in human fertility is predictable and can be quantified. Indeed, various authors have demonstrated that the downturn in women's fertility is the consequence of an age-dependent reduction in the number of remaining follicles, which starts during embryogenesis and continues. The initial pool of primordial follicles—at 16 to 20 weeks of fetal life—is believed to encompass approximately 6 to 7 million oocytes. At birth, the female's ovaries contain only 2 million oocytes, and by menarche, about 300,000 remain.2 That number is more than sufficient, as only about 450 monofollicular ovulations are required during a reproductive life of approximately 30 years.
Yet the number of remaining follicles does appear to matter, because when the follicular count falls to about 25,000—as it does in a physiologically normal ovary at approximately age 37.5—the decline in follicular numbers accelerates.3 Various authors, therefore, have suggested that what determines when a woman will experience menopause is not her age but how quickly her follicular count drops to approximately 1,000, the quantity at which menopause usually occurs.4 On average, that happens at age 51, or about 13 years after a woman reaches the 25,000-follicle milestone. In other words, at about age 37.5, a woman's fertility begins to accelerate, and about 13 years later, menopause sets in.
Age-Related Analysis of Inhibin A, Inhibin B
Relative to the Intercycle Monotropic Follicle-Stimulating Hormone Rise in Normal Ovulatory Women
Nancy A. Klein, Brenda S. Houmard, Karl R. Hansen, Teresa K. Woodruff, Patrick M. Sluss, William J. Bremner and Michael R. Soules
Previous studies have reported that the monotropic rise in FSH in older women is associated with decreased inhibin B and/or A levels and increased levels of activin A. Whereas most investigators have found decreased follicular-phase inhibin B, the roles of inhibin A and activin A as modulators of the FSH rise are unclear. The objectives of this study were to determine whether deficiencies in circulating levels of inhibin A, inhibin B, and/or activin A exist during the intercycle interval in ovulatory older (age, 40–45 yr; n = 16), compared with younger women (age, 20–25 yr; n = 13). Blood samples were obtained daily throughout one menstrual cycle and the follicular phase of the subsequent cycle and were analyzed for LH, FSH, estradiol, inhibin A and B, and activin A. Despite significant FSH elevation, no deficiencies in inhibin A, activin A, or estradiol were detected in older subjects. In fact, inhibin A was significantly higher in older participants during the intercycle phase (P = 0.01), whereas inhibin B was significantly lower. Thus, the monotropic rise in FSH does not appear to result from changes in inhibin A or activin A, supporting the concept that inhibin B plays a critical role in mediating the FSH rise in older women.
Nancy A. Klein, Brenda S. Houmard, Karl R. Hansen, Teresa K. Woodruff, Patrick M. Sluss, William J. Bremner and Michael R. Soules
Previous studies have reported that the monotropic rise in FSH in older women is associated with decreased inhibin B and/or A levels and increased levels of activin A. Whereas most investigators have found decreased follicular-phase inhibin B, the roles of inhibin A and activin A as modulators of the FSH rise are unclear. The objectives of this study were to determine whether deficiencies in circulating levels of inhibin A, inhibin B, and/or activin A exist during the intercycle interval in ovulatory older (age, 40–45 yr; n = 16), compared with younger women (age, 20–25 yr; n = 13). Blood samples were obtained daily throughout one menstrual cycle and the follicular phase of the subsequent cycle and were analyzed for LH, FSH, estradiol, inhibin A and B, and activin A. Despite significant FSH elevation, no deficiencies in inhibin A, activin A, or estradiol were detected in older subjects. In fact, inhibin A was significantly higher in older participants during the intercycle phase (P = 0.01), whereas inhibin B was significantly lower. Thus, the monotropic rise in FSH does not appear to result from changes in inhibin A or activin A, supporting the concept that inhibin B plays a critical role in mediating the FSH rise in older women.
The 13 Year Window
The premise brought forth (Nicolaou and Templeton, 2003Go) is that there is a 13-year window between the beginning of the accelerated phase of atresia (38 years) and the average age of menopause (51 years).
Nikolaou, D. and Templeton, A. (2003) Early ovarian ageing: a hypothesis. Detection and clinical relevance. Hum. Reprod., 18, 1137–1139
There are two general concerns challenging this hypothesis.....
The second issue is the ‘fixed’ nature of this window of 13 years. Basically, we just do not know if this is the case. While it was originally assumed that oocyte loss occurred as a constant logarithmic function (Block, 1952Go), it is more accepted now that there is an accelerated depletion after age 38 years (Richardson et al., 1987Go; Gougeon et al., 1994Go).
Block, E. (1952) Quantitative morphological investigation of the follicular system in women. Acta Anat., 14, 108–123
Richardson, S.J., Senikas, V. and Nelson, J.F. (1987) Follicular depletion during the menopausal transition. Evidence for accelerated loss and ultimate exhaustion. J. Clin. Endocrinol. Metab., 65, 1231–1237
Gougeon, A., Ecochard, R. and Thalabard, J.C. (1994) Age-related changes of the population of human ovarian follicles: Increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol. Reprod., 50, 653–663.
However, it is not at all clear what the variability is in the slope of this line. Rate of atresia may be variable in different women, and this variability may occur before age 38, as well as in the time period after age 38. At least two conditions have been theorized to alter (increase) the rate of atresia (genetic variations in the X chromosome and thymectomy) (Singh and Carr, 1966Go; Lintern-Moore, 1977Go)
The 13-year window (which is assumed to be the average time frame for women) may not be 13 years per se and is likely to be less or more on an individual basis.
Nikolaou, D. and Templeton, A. (2003) Early ovarian ageing: a hypothesis. Detection and clinical relevance. Hum. Reprod., 18, 1137–1139
There are two general concerns challenging this hypothesis.....
The second issue is the ‘fixed’ nature of this window of 13 years. Basically, we just do not know if this is the case. While it was originally assumed that oocyte loss occurred as a constant logarithmic function (Block, 1952Go), it is more accepted now that there is an accelerated depletion after age 38 years (Richardson et al., 1987Go; Gougeon et al., 1994Go).
Block, E. (1952) Quantitative morphological investigation of the follicular system in women. Acta Anat., 14, 108–123
Richardson, S.J., Senikas, V. and Nelson, J.F. (1987) Follicular depletion during the menopausal transition. Evidence for accelerated loss and ultimate exhaustion. J. Clin. Endocrinol. Metab., 65, 1231–1237
Gougeon, A., Ecochard, R. and Thalabard, J.C. (1994) Age-related changes of the population of human ovarian follicles: Increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol. Reprod., 50, 653–663.
However, it is not at all clear what the variability is in the slope of this line. Rate of atresia may be variable in different women, and this variability may occur before age 38, as well as in the time period after age 38. At least two conditions have been theorized to alter (increase) the rate of atresia (genetic variations in the X chromosome and thymectomy) (Singh and Carr, 1966Go; Lintern-Moore, 1977Go)
The 13-year window (which is assumed to be the average time frame for women) may not be 13 years per se and is likely to be less or more on an individual basis.
The Impact of age on Female Fertility
BACKGROUND
Over the past several decades, demographic and socioeconomic trends have resulted in an increase in the absolute number of women seeking pregnancy in their late 30’s and early to mid-40’s. In addition, a significant number of women in this age group are seeking evaluation and treatment for infertility. Although there is a very well demonstrated decline in female fertility as a function of age, this phenomenon has typically has been under-recognized not only by the general population, but also by many health care providers. This is probably related to the fact that in previous decades women generally had completed childbearing by the late 30’s and in fact many of the pregnancies that occurred in the later reproductive years were unplanned. An increased awareness of the effects of aging on fertility for patients and health care providers is critical to the prevention of age-related infertility.
continue reading
Age and Infertility. The Biological Clock, fact or fiction?
With recent dramatic advances in infertility treatment, age related infertility remains as one of our most difficult challenges. Reproductive specialists have known for years that the pregnancy rate is inversely related to the female partner's age. Early explanations for this trend included decreased coital frequency, diminished desire for childbearing, decreased overall time to try for a pregnancy, and diminished ovarian reserve with advancing age.1,2 Today, we would add increased spontaneous abortion, oocyte depletion, and oocyte aging to the list.3 Coupling this issue of age with our current societal trend of increased numbers of women who delay childbearing for educational and career goals, we now have a dramatic increase in age related infertility. For those providing primary care to women, it is now much more important to carefully counsel patients regarding family planning issues, especially with regards to advancing age and diminished pregnancy rates. Patients who are in their early to mid thirties or beyond who are considering pregnancy or have been trying for any length of time without success warrant an early referral for evaluation.
Over the past several decades, demographic and socioeconomic trends have resulted in an increase in the absolute number of women seeking pregnancy in their late 30’s and early to mid-40’s. In addition, a significant number of women in this age group are seeking evaluation and treatment for infertility. Although there is a very well demonstrated decline in female fertility as a function of age, this phenomenon has typically has been under-recognized not only by the general population, but also by many health care providers. This is probably related to the fact that in previous decades women generally had completed childbearing by the late 30’s and in fact many of the pregnancies that occurred in the later reproductive years were unplanned. An increased awareness of the effects of aging on fertility for patients and health care providers is critical to the prevention of age-related infertility.
continue reading
Age and Infertility. The Biological Clock, fact or fiction?
With recent dramatic advances in infertility treatment, age related infertility remains as one of our most difficult challenges. Reproductive specialists have known for years that the pregnancy rate is inversely related to the female partner's age. Early explanations for this trend included decreased coital frequency, diminished desire for childbearing, decreased overall time to try for a pregnancy, and diminished ovarian reserve with advancing age.1,2 Today, we would add increased spontaneous abortion, oocyte depletion, and oocyte aging to the list.3 Coupling this issue of age with our current societal trend of increased numbers of women who delay childbearing for educational and career goals, we now have a dramatic increase in age related infertility. For those providing primary care to women, it is now much more important to carefully counsel patients regarding family planning issues, especially with regards to advancing age and diminished pregnancy rates. Patients who are in their early to mid thirties or beyond who are considering pregnancy or have been trying for any length of time without success warrant an early referral for evaluation.
Here's Another One
"As expected, advancing female age was strongly associated with reduced fertility. The day-specific probabilities of pregnancy were observed to decline in women in their late 20s, slightly earlier than reported in the CECOS study of women with artificial insemination (Fédération CECOS, 1982). Nearly a 50% drop occurred between women in their early 20s and women in their late 30s. These estimates do not include the increased occurrence of spontaneous abortion that is evident in older women, but do include early, preclinical loss, which is not distinguishable from non-conception in these data."
Changes with age in the level and duration of fertility in the menstrual cycle
David B. Dunson1, Bernardo Colombo and Donna D. Baird
Here the CECOS study:
Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands. Federation CECOS.
Schwartz D, Mayaux MJ.
PIP: Fecundity has been reported to decline in women over 30 years of age. It is not known whether the decrease in fecundity is biologic or simply the consequence of diminished sexual activity. Artificial insemination with donor semen (AID) offers an opportunity to control certain variables in the study of female fecundity over time. 2193 nulliparous women who were receiving AID from 1973-80 at the Centres d'Etude et de Conservation du Sperme Humain (CECOS) and whose husbands were totally sterile were studied. The women were divided into 4 age groups: 25 years old or younger (n=371), 26-30 (n=1079), 31-35 (n=599), and 35 or older (n=144). At the end of the study period, the women were categorized into 4 groups, depending on the outcome: success (all pregnancies occurring during the study period), lost to follow-up (if the result of the last AID cycle was unknown), open case (result of last AID cycle was known but the next insemination procedure had not yet taken place), and dropout (discontinued treatment). The cumulative success rates were calculated ater 12 cycles with the life table technique adapted to AID as if there were no dropouts (theoretical cumulative rates). The Mantel-Haenzel test was used to compare the curves obtained from the cumulative rate as a function of the number of treatment cycles for the various age groups. The 4 curves differed significantly (chi-square=15.72, with 3 degrees of freedom; p0.01). The curves for the 2 age groups under 30 were very similar. Overall, the study shows that a decrease in fecundability (conception rate per cycle) as a function of a woman's age is slight but significant after 30 years of age and marked after 35 years. The probability of success of AID for 12 cycles declined to 61% (from 73% for those under 31 years old) for the 31-35 age group (p0.03) and to 54% (from 74% for those under 31 years old) for those over 35 (p0.001). 2 major problems encountered in studying variations in fecundity as a function of a woman's age are: 1) the need to separate the effect of the woman's age from associated variables such as coital pattern and husband's age, and 2) the woman's age itself, which could result in bias, since time introduces a type of selection. AID may provide the best means of minimizing the effects of associated variables and sources of bias.
Changes with age in the level and duration of fertility in the menstrual cycle
David B. Dunson1, Bernardo Colombo and Donna D. Baird
Here the CECOS study:
Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands. Federation CECOS.
Schwartz D, Mayaux MJ.
PIP: Fecundity has been reported to decline in women over 30 years of age. It is not known whether the decrease in fecundity is biologic or simply the consequence of diminished sexual activity. Artificial insemination with donor semen (AID) offers an opportunity to control certain variables in the study of female fecundity over time. 2193 nulliparous women who were receiving AID from 1973-80 at the Centres d'Etude et de Conservation du Sperme Humain (CECOS) and whose husbands were totally sterile were studied. The women were divided into 4 age groups: 25 years old or younger (n=371), 26-30 (n=1079), 31-35 (n=599), and 35 or older (n=144). At the end of the study period, the women were categorized into 4 groups, depending on the outcome: success (all pregnancies occurring during the study period), lost to follow-up (if the result of the last AID cycle was unknown), open case (result of last AID cycle was known but the next insemination procedure had not yet taken place), and dropout (discontinued treatment). The cumulative success rates were calculated ater 12 cycles with the life table technique adapted to AID as if there were no dropouts (theoretical cumulative rates). The Mantel-Haenzel test was used to compare the curves obtained from the cumulative rate as a function of the number of treatment cycles for the various age groups. The 4 curves differed significantly (chi-square=15.72, with 3 degrees of freedom; p0.01). The curves for the 2 age groups under 30 were very similar. Overall, the study shows that a decrease in fecundability (conception rate per cycle) as a function of a woman's age is slight but significant after 30 years of age and marked after 35 years. The probability of success of AID for 12 cycles declined to 61% (from 73% for those under 31 years old) for the 31-35 age group (p0.03) and to 54% (from 74% for those under 31 years old) for those over 35 (p0.001). 2 major problems encountered in studying variations in fecundity as a function of a woman's age are: 1) the need to separate the effect of the woman's age from associated variables such as coital pattern and husband's age, and 2) the woman's age itself, which could result in bias, since time introduces a type of selection. AID may provide the best means of minimizing the effects of associated variables and sources of bias.
Here It Is!
Follicle dynamics during ovarian ageing.
Faddy MJ
Mol Cell Endocrinol. 2000 May 25;163(1-2):43-8.
The human ovary is endowed at birth with a fixed number of primordial follicles which steadily declines throughout life as a result of atresia and recruitment towards ovulation. The pattern of this decline is not exponential, but more bi-exponential corresponding to a 'broken-stick' regression of logged total numbers of follicles against age. Such a model implies an abrupt change in the exponential rate of follicle loss at age 38 years, and is thus rather implausible biologically. A more refined model with an exponential rate of follicle loss that changes gradually throughout life also describes the data on declining follicle numbers but in addition leads to a distribution of age at menopause, corresponding to follicle numbers falling below a critical threshold, that shows quite remarkable agreement with independent data on menopausal ages of American women. When the follicles are classified into resting and growing stages, it is found that any changes in the consequent process of follicle development as the ovary ages relate mainly to the small resting follicles and not the larger growing ones.
Power point presentation:
Premature Ovarian Aging and Infertility
Faddy MJ
Mol Cell Endocrinol. 2000 May 25;163(1-2):43-8.
The human ovary is endowed at birth with a fixed number of primordial follicles which steadily declines throughout life as a result of atresia and recruitment towards ovulation. The pattern of this decline is not exponential, but more bi-exponential corresponding to a 'broken-stick' regression of logged total numbers of follicles against age. Such a model implies an abrupt change in the exponential rate of follicle loss at age 38 years, and is thus rather implausible biologically. A more refined model with an exponential rate of follicle loss that changes gradually throughout life also describes the data on declining follicle numbers but in addition leads to a distribution of age at menopause, corresponding to follicle numbers falling below a critical threshold, that shows quite remarkable agreement with independent data on menopausal ages of American women. When the follicles are classified into resting and growing stages, it is found that any changes in the consequent process of follicle development as the ovary ages relate mainly to the small resting follicles and not the larger growing ones.
Power point presentation:
Premature Ovarian Aging and Infertility
Fetal Growth Retardation and Ovarian Development
Fetal growth retardation as a cause of impaired ovarian development
J. P. de Bruina, M. Dorlanda, H. W. Bruinsea, W. Splietb, P. G. J. Nikkelsb and E. R. Te Veldea
Abstract
Low birthweight has been associated with diseases and disorders later in life. It has been suggested that this is caused by the impaired development of abdominal organs, especially in cases of growth retardation. Besides general malnutrition of the fetus, preferential bloodflow to the heart and brain may further deprive organs, such as liver, pancreas and kidney, of nutrients. As a result these organs may not develop properly. Anatomically, the ovary is situated close to the kidney and it is very likely that, similar to the kidney, ovarian development can be negatively affected by intra-uterine growth retardation. Placental insufficiency, which is an important cause of severe intra-uterine growth retardation, was used as a model to investigate this hypothesis. In the present study, the volume percentages of primordial follicles in the ovaries of four severely growth-retarded fetuses of different gestational ages are compared to those of four age-matched controls. It is found that these volume percentages in growth-retarded fetuses were significantly lower than those observed in the age-matched controls. It can be concluded that ovarian development is impaired in intra-uterine growth-retarded fetuses. These findings further suggest that, as a result of the premature loss of follicles, females with low birthweights may encounter fertility problems later in life.
Morphometry of human ovaries in normal and growth-restricted fetuses
J. P. de BruinCorresponding Author Contact Information, E-mail The Corresponding Author, a, P. G. J. Nikkelsb, H. W. Bruinsec, M. van Haaftena, C. W. N. Loomand and E. R. te Veldec
Abstract
According to the fetal origins hypothesis, normal growth and development of abdominal organs is disturbed by intra-uterine growth restriction, leading to diseases later in life. The aims of this study were to investigate the effect of growth restriction on the ovaries of human fetuses and to investigate the dynamics of follicular growth in normal fetuses. We selected 21 normal female fetuses (controls) and seven severely intra-uterine growth-restricted female fetuses (IUGR cases) from all autopsy records over a 10-year period. Ovarian volume was calculated and from histological sections the volume-percentage of follicles in the ovarian cortex, the maximum diameters of individual follicles and the distribution of the follicle classes and oogonia were determined. The volume of the ovaries increased significantly from 0.10 to 0.36 cm3 in the second half of gestation. The mean volume-percentage of ovarian follicles and the mean follicle diameter significantly increased with 0.48% and 0.52 μm per week, respectively. Class B/C (intermediary) follicles (72%) were predominantly present. Class B (primordial) follicles decreased from over 20% to less than 10% and class C (primary) increased from 6 to 19%. Class A (oogonia) were frequently present before 30 gestational weeks, but were rare after that age. For all studied parameters we did not find differences between IUGR cases and controls. Intra-uterine growth restriction does not seem to disturb ovarian development in the human fetus. In the second half of gestation the follicle pool increases by the growth of individual follicles, the transition of follicle to larger classes, and probably by increasing follicle numbers. As most follicles at term were class B/C and C, follicles up to class C are probably part of the resting stock.
Aspects of Ovarian Follicle Development throughout Life, N.S. Macklon, B.C.J.M. Fauser
Abstract
The pool of primordial follicles present in the female ovary reaches its maximum number around 20 weeks of gestational age and then decreases in a logarithmic fashion throughout life until complete depletion occurs around the age of the menopause. Reproductive life is initiated when less than 10% (0.5 million) of primordial follicles are left. The entire growth trajectory of the follicle takes at least 3 months. Follicle growth up to the antral stage occurs during fetal life and infancy. While the role of gonadotropins in early follicular development remains controversial, the last 2 weeks of development are FSH dependent. The intercycle rise in FSH and decreasing levels thereafter are crucial for recruitment of a cohort of healthy, early antral follicles and subsequent single dominant selection. Following puberty, anovulation may persist for years and this may presage the development of adult anovulatory infertility. The menopause is preceded by a period of reduced fertility. The development of reliable and sensitive markers for ovarian ageing will be the challenge of the near future.
J. P. de Bruina, M. Dorlanda, H. W. Bruinsea, W. Splietb, P. G. J. Nikkelsb and E. R. Te Veldea
Abstract
Low birthweight has been associated with diseases and disorders later in life. It has been suggested that this is caused by the impaired development of abdominal organs, especially in cases of growth retardation. Besides general malnutrition of the fetus, preferential bloodflow to the heart and brain may further deprive organs, such as liver, pancreas and kidney, of nutrients. As a result these organs may not develop properly. Anatomically, the ovary is situated close to the kidney and it is very likely that, similar to the kidney, ovarian development can be negatively affected by intra-uterine growth retardation. Placental insufficiency, which is an important cause of severe intra-uterine growth retardation, was used as a model to investigate this hypothesis. In the present study, the volume percentages of primordial follicles in the ovaries of four severely growth-retarded fetuses of different gestational ages are compared to those of four age-matched controls. It is found that these volume percentages in growth-retarded fetuses were significantly lower than those observed in the age-matched controls. It can be concluded that ovarian development is impaired in intra-uterine growth-retarded fetuses. These findings further suggest that, as a result of the premature loss of follicles, females with low birthweights may encounter fertility problems later in life.
Morphometry of human ovaries in normal and growth-restricted fetuses
J. P. de BruinCorresponding Author Contact Information, E-mail The Corresponding Author, a, P. G. J. Nikkelsb, H. W. Bruinsec, M. van Haaftena, C. W. N. Loomand and E. R. te Veldec
Abstract
According to the fetal origins hypothesis, normal growth and development of abdominal organs is disturbed by intra-uterine growth restriction, leading to diseases later in life. The aims of this study were to investigate the effect of growth restriction on the ovaries of human fetuses and to investigate the dynamics of follicular growth in normal fetuses. We selected 21 normal female fetuses (controls) and seven severely intra-uterine growth-restricted female fetuses (IUGR cases) from all autopsy records over a 10-year period. Ovarian volume was calculated and from histological sections the volume-percentage of follicles in the ovarian cortex, the maximum diameters of individual follicles and the distribution of the follicle classes and oogonia were determined. The volume of the ovaries increased significantly from 0.10 to 0.36 cm3 in the second half of gestation. The mean volume-percentage of ovarian follicles and the mean follicle diameter significantly increased with 0.48% and 0.52 μm per week, respectively. Class B/C (intermediary) follicles (72%) were predominantly present. Class B (primordial) follicles decreased from over 20% to less than 10% and class C (primary) increased from 6 to 19%. Class A (oogonia) were frequently present before 30 gestational weeks, but were rare after that age. For all studied parameters we did not find differences between IUGR cases and controls. Intra-uterine growth restriction does not seem to disturb ovarian development in the human fetus. In the second half of gestation the follicle pool increases by the growth of individual follicles, the transition of follicle to larger classes, and probably by increasing follicle numbers. As most follicles at term were class B/C and C, follicles up to class C are probably part of the resting stock.
Aspects of Ovarian Follicle Development throughout Life, N.S. Macklon, B.C.J.M. Fauser
Abstract
The pool of primordial follicles present in the female ovary reaches its maximum number around 20 weeks of gestational age and then decreases in a logarithmic fashion throughout life until complete depletion occurs around the age of the menopause. Reproductive life is initiated when less than 10% (0.5 million) of primordial follicles are left. The entire growth trajectory of the follicle takes at least 3 months. Follicle growth up to the antral stage occurs during fetal life and infancy. While the role of gonadotropins in early follicular development remains controversial, the last 2 weeks of development are FSH dependent. The intercycle rise in FSH and decreasing levels thereafter are crucial for recruitment of a cohort of healthy, early antral follicles and subsequent single dominant selection. Following puberty, anovulation may persist for years and this may presage the development of adult anovulatory infertility. The menopause is preceded by a period of reduced fertility. The development of reliable and sensitive markers for ovarian ageing will be the challenge of the near future.
Lourdes Ibañez, Menarche and Low Birth Weight
I am currently looking at lower age at menarche, speed of transition to the lower ages, and fertility impacts. The big conjecture would be that there should be a negative impact of this process on final achieved TFRs in the context of a systematic and continuing birth postponment process. To date I have nothing conclusive on this one way or the other.
However I have identified two secondary feedback mechanisms which do seem to influence long term fertility:
a) A correlation between obesity and lowest low menarche. Now obestity is also a fertility inhibiting correlate.
b) A relationship between reduced birth weight, lower age at menarche (due to subsequent cath-up growth) and reduced lifelong fertility.
Here the work of Lourdes Ibañez seem to be very important:
Early Puberty-Menarche After Precocious Pubarche: Relation to Prenatal Growth
Lourdes Ibáñez, MD, PhDa, Rafael Jiménez, MD, PhDa and Francis de Zegher, MD, PhDb
RESULTS. At the time of PP diagnosis, age, bone age, and BMI were similar across birth weight subgroups; circulating sex hormone–binding globulin and body height were reduced in PP girls with lower birth weight, and these remained so throughout pubertal development. Onset of puberty occurred earlier in PP girls with lower birth weight; so did menarche. Adult height differed by an average of 6.5 cm (~1 SD) between the upper and lower birth weight subgroups; this difference was essentially achieved before puberty and even before PP. Menarche before age 12.0 years was twofold more prevalent in PP girls than in control subjects. Among PP girls, age at menarche was advanced by 8 to 10 months in lower versus higher birth weight girls. Menarche before age 12.0 years was threefold more prevalent among LBW-PP girls than in control subjects (~75% vs ~25%).
CONCLUSIONS. The link between prenatal growth restraint and early menarche is herewith extended to PP girls. In particular LBW-PP girls may become a target group for interventions directed toward normalization of pubertal onset and progression.
Reduced Ovulation Rate in Adolescent Girls Born Small for Gestational Age
Lourdes Ibáñez, Neus Potau, Angela Ferrer, Francisco Rodriguez-Hierro, Maria Victoria Marcos and Francis de Zegher
Interestingly for the bigger issue Lourdes here finds a more rapid ovulation rate in post menarche children than previously reported:
"This is a first study assessing adolescent ovulation rate over 3 months, on an ambulatory basis, through weekly measurements of progesterone concentrations in capillary blood dried on filter paper. With this novel method, 23 of 24 participating AGA (appropriate for gestational age) girls were found to have at least one ovulatory cycle within 3 months. This ovulation rate (96%) is, so far, the highest reported in adolescents (16, 17), suggesting that this technique has a sensitivity superior to previous methods (17). Moreover, it is unlikely that this simple method overestimates ovulation rate because the time lag between the proposed ovulation date and the onset of the following menses was uniformly consistent with the time course of a normal ovulatory cycle."
However:
"The ovulation rate in SGA (small for gestational age) girls was found to be strikingly low; the anovulatory fraction was much larger than in the AGA girls. Moreover, in ovulatory SGA girls, the individual number of ovulations over 3 months was also reduced. Interestingly, the reduction in ovulation rate was comparable in SGA adolescents who had reached a stature within target range and in SGA girls with a postmenarcheal stature that was below target level. This observation suggests that anovulation secondary to prenatal growth restraint is a phenomenon that is essentially unrelated to completeness of spontaneous catch-up growth. Thus, in SGA girls, spontaneous recovery of linear growth during childhood does not warrant normal ovulatory function in adolescence; conversely, persistent growth failure in SGA girls will not necessarily be followed by anovulation."
"That the link between reduced prenatal growth and anovulation has apparently escaped attention for so long may in part be attributable to the fact that the majority of SGA girls normalize their stature, and hereby no longer present an obvious reminder of their early growth restraint. The copresence of obesity may have been another notoriously confounding factor in ovulation research; the absence of obesity in the described study population has presumably facilitated the disclosure of the link between prenatal growth and postmenarcheal ovulation rate."
"Prenatal growth restraint has previously been documented to be associated with relative hyperinsulinism, hyperandrogenism, and FSH hypersecretion in adolescent girls from Catalunya (5, 18, 19). These associations were confirmed in the present cohort and may each contribute to the reduced ovulation rate in SGA adolescents."
Ibáñez L, Potau N, de Zegher F 2000 Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab 85:2624–2626
Ibáñez L, Potau N, Marcos MV, de Zegher F 1999 Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 84:4739–4741
Ibáñez L, Valls C, Miró E, Marcos MV, de Zegher F Early menarche and subclinical ovarian hyperandrogenism in girls with reduced adult height after low birthweight. J Pediatr Endocrinol Metab 15:431–433
Ibáñez L, Valls C, Ferrer A, Ong K, Dunger D, de Zegher F 2002 Additive effects of insulin-sensitizing and anti-androgen treatment in young, non-obese women with hyperinsulinism, hyperandrogenism, dyslipidemia and anovulation. J Clin Endocrinol Metab 87:2870–2874
"In conclusion, the endocrine correlates of prenatal growth restraint are herewith extended to include oligo-ovulation and anovulation in adolescence. It remains to be verified whether this SGA-related phenomenon persists into the reproductive age range. If it does, then fetal growth restraint may prove to be one of the enigmatic components underpinning hitherto unexplained female subfertility."
Here's a page summarising Lourdes's work (in Catalan).
However I have identified two secondary feedback mechanisms which do seem to influence long term fertility:
a) A correlation between obesity and lowest low menarche. Now obestity is also a fertility inhibiting correlate.
b) A relationship between reduced birth weight, lower age at menarche (due to subsequent cath-up growth) and reduced lifelong fertility.
Here the work of Lourdes Ibañez seem to be very important:
Early Puberty-Menarche After Precocious Pubarche: Relation to Prenatal Growth
Lourdes Ibáñez, MD, PhDa, Rafael Jiménez, MD, PhDa and Francis de Zegher, MD, PhDb
RESULTS. At the time of PP diagnosis, age, bone age, and BMI were similar across birth weight subgroups; circulating sex hormone–binding globulin and body height were reduced in PP girls with lower birth weight, and these remained so throughout pubertal development. Onset of puberty occurred earlier in PP girls with lower birth weight; so did menarche. Adult height differed by an average of 6.5 cm (~1 SD) between the upper and lower birth weight subgroups; this difference was essentially achieved before puberty and even before PP. Menarche before age 12.0 years was twofold more prevalent in PP girls than in control subjects. Among PP girls, age at menarche was advanced by 8 to 10 months in lower versus higher birth weight girls. Menarche before age 12.0 years was threefold more prevalent among LBW-PP girls than in control subjects (~75% vs ~25%).
CONCLUSIONS. The link between prenatal growth restraint and early menarche is herewith extended to PP girls. In particular LBW-PP girls may become a target group for interventions directed toward normalization of pubertal onset and progression.
Reduced Ovulation Rate in Adolescent Girls Born Small for Gestational Age
Lourdes Ibáñez, Neus Potau, Angela Ferrer, Francisco Rodriguez-Hierro, Maria Victoria Marcos and Francis de Zegher
Interestingly for the bigger issue Lourdes here finds a more rapid ovulation rate in post menarche children than previously reported:
"This is a first study assessing adolescent ovulation rate over 3 months, on an ambulatory basis, through weekly measurements of progesterone concentrations in capillary blood dried on filter paper. With this novel method, 23 of 24 participating AGA (appropriate for gestational age) girls were found to have at least one ovulatory cycle within 3 months. This ovulation rate (96%) is, so far, the highest reported in adolescents (16, 17), suggesting that this technique has a sensitivity superior to previous methods (17). Moreover, it is unlikely that this simple method overestimates ovulation rate because the time lag between the proposed ovulation date and the onset of the following menses was uniformly consistent with the time course of a normal ovulatory cycle."
However:
"The ovulation rate in SGA (small for gestational age) girls was found to be strikingly low; the anovulatory fraction was much larger than in the AGA girls. Moreover, in ovulatory SGA girls, the individual number of ovulations over 3 months was also reduced. Interestingly, the reduction in ovulation rate was comparable in SGA adolescents who had reached a stature within target range and in SGA girls with a postmenarcheal stature that was below target level. This observation suggests that anovulation secondary to prenatal growth restraint is a phenomenon that is essentially unrelated to completeness of spontaneous catch-up growth. Thus, in SGA girls, spontaneous recovery of linear growth during childhood does not warrant normal ovulatory function in adolescence; conversely, persistent growth failure in SGA girls will not necessarily be followed by anovulation."
"That the link between reduced prenatal growth and anovulation has apparently escaped attention for so long may in part be attributable to the fact that the majority of SGA girls normalize their stature, and hereby no longer present an obvious reminder of their early growth restraint. The copresence of obesity may have been another notoriously confounding factor in ovulation research; the absence of obesity in the described study population has presumably facilitated the disclosure of the link between prenatal growth and postmenarcheal ovulation rate."
"Prenatal growth restraint has previously been documented to be associated with relative hyperinsulinism, hyperandrogenism, and FSH hypersecretion in adolescent girls from Catalunya (5, 18, 19). These associations were confirmed in the present cohort and may each contribute to the reduced ovulation rate in SGA adolescents."
Ibáñez L, Potau N, de Zegher F 2000 Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab 85:2624–2626
Ibáñez L, Potau N, Marcos MV, de Zegher F 1999 Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 84:4739–4741
Ibáñez L, Valls C, Miró E, Marcos MV, de Zegher F Early menarche and subclinical ovarian hyperandrogenism in girls with reduced adult height after low birthweight. J Pediatr Endocrinol Metab 15:431–433
Ibáñez L, Valls C, Ferrer A, Ong K, Dunger D, de Zegher F 2002 Additive effects of insulin-sensitizing and anti-androgen treatment in young, non-obese women with hyperinsulinism, hyperandrogenism, dyslipidemia and anovulation. J Clin Endocrinol Metab 87:2870–2874
"In conclusion, the endocrine correlates of prenatal growth restraint are herewith extended to include oligo-ovulation and anovulation in adolescence. It remains to be verified whether this SGA-related phenomenon persists into the reproductive age range. If it does, then fetal growth restraint may prove to be one of the enigmatic components underpinning hitherto unexplained female subfertility."
Here's a page summarising Lourdes's work (in Catalan).
Saturday, June 03, 2006
China Menarche II
"Southern Chinese girls aged 11 years and 9 months to 12 years and 3
months in Hong Kong have a mean menarcheal age of 11.50 years
(standard deviation of 0.47) using the recollection method. Highly
significant differences are found when compared to the 12-year-old
girls in Hong Kong studied in the past decades. Therefore, a secular
trend of earlier menarcheal age is demonstrated.
So, LL, Yen, PK. Secular trend of menarcheal age in southern Chinese girls.
Z Morphol Anthropol. 1992 Jun;79(1):21-4.
Huen, KF, Leung, SS, Lau, JT, Cheung, AY, Leung, NK, Chiu, MC. Secular
trend in the sexual maturation of southern Chinese girls. Acta
Paediatr. 1997 Oct;86(10):1121-4.
"In 1993, a cross-sectional study of sexual maturation of normal
Chinese schoolgirls was performed in Hong Kong. The aim of the study
was to obtain an up-to-date reference for normal pubertal development
in Chinese girls. ... Menstrual status was recorded in 6467 girls over
6 y of age. ... The median age of menarche was 12.38 (95% CI
11.98-12.78) years. ... When comparison is made with similar studies
done in 1962 and 1979, a significant downward secular trend in sexual
maturation is observed (p < 0.01). Except for breast development the
downward secular trend in sexual maturation appears to be diminishing
and may be coming to a halt in the Chinese girls in Hong Kong. Their
median ages of sexual maturation are now among one of the earliest
medians recorded in the world population studied."
Growth status and menarche in urban and rural China
T. Hesketh, Qu Jian Ding, A. Tomkins
Abstract:
Objective: To examine the relationship between current age at menarche and growth status in an urban and rural area of Eastern China. Study design: Cross-sectional survey: self-completion questionnaire and anthropometry in 12 schools in urban Hangzhou and rural Chunan in Zhejiang Province. Results: The median menarcheal age calculated by probit analysis was significantly different in the two areas: 12.8 years (SD 0.9) in the urban area and 13.2 (SD 1.0) in the rural area (p < 0.001). Girls who reach menarche are significantly heavier and taller with higher BMIs than those of the same age who are pre-menarche. After adjustment for BMI and other possible confounders, urban girls were still menstruating significantly earlier than girls in rural areas (OR 3.3, 2.1-5.2). Conclusions: The age of menarche is probably still declining in China. Although BMI is an important factor in the onset of menstruation, some other unmeasured environmental variable may be implicated in this population.
months in Hong Kong have a mean menarcheal age of 11.50 years
(standard deviation of 0.47) using the recollection method. Highly
significant differences are found when compared to the 12-year-old
girls in Hong Kong studied in the past decades. Therefore, a secular
trend of earlier menarcheal age is demonstrated.
So, LL, Yen, PK. Secular trend of menarcheal age in southern Chinese girls.
Z Morphol Anthropol. 1992 Jun;79(1):21-4.
Huen, KF, Leung, SS, Lau, JT, Cheung, AY, Leung, NK, Chiu, MC. Secular
trend in the sexual maturation of southern Chinese girls. Acta
Paediatr. 1997 Oct;86(10):1121-4.
"In 1993, a cross-sectional study of sexual maturation of normal
Chinese schoolgirls was performed in Hong Kong. The aim of the study
was to obtain an up-to-date reference for normal pubertal development
in Chinese girls. ... Menstrual status was recorded in 6467 girls over
6 y of age. ... The median age of menarche was 12.38 (95% CI
11.98-12.78) years. ... When comparison is made with similar studies
done in 1962 and 1979, a significant downward secular trend in sexual
maturation is observed (p < 0.01). Except for breast development the
downward secular trend in sexual maturation appears to be diminishing
and may be coming to a halt in the Chinese girls in Hong Kong. Their
median ages of sexual maturation are now among one of the earliest
medians recorded in the world population studied."
Growth status and menarche in urban and rural China
T. Hesketh, Qu Jian Ding, A. Tomkins
Abstract:
Objective: To examine the relationship between current age at menarche and growth status in an urban and rural area of Eastern China. Study design: Cross-sectional survey: self-completion questionnaire and anthropometry in 12 schools in urban Hangzhou and rural Chunan in Zhejiang Province. Results: The median menarcheal age calculated by probit analysis was significantly different in the two areas: 12.8 years (SD 0.9) in the urban area and 13.2 (SD 1.0) in the rural area (p < 0.001). Girls who reach menarche are significantly heavier and taller with higher BMIs than those of the same age who are pre-menarche. After adjustment for BMI and other possible confounders, urban girls were still menstruating significantly earlier than girls in rural areas (OR 3.3, 2.1-5.2). Conclusions: The age of menarche is probably still declining in China. Although BMI is an important factor in the onset of menstruation, some other unmeasured environmental variable may be implicated in this population.
Germany Menarche
Changes in age at menarche in Germany: Evidence for a continuing decline
Dörte Ostersehlt, Heidi Danker-Hopfe
Abstract
Since there are no recent data on secular changes in growth and maturation of girls from West Germany, two cross-sectional studies with equal design have been carried out in Bremerhaven, North Germany, in 1979/80 and 1989. The present paper presents the results of an analysis of changes in age at menarche based on status quo data from school girls (1979/80: 2,796; 1989: 2,223) aged between 10.0 and 18.5 years. Probit analyses show a reduction over the 10-year period from 13.30 ± 1.19 to 13.01 ± 1.21 years, while logit analyses, which fit the empirical data slightly better, show a reduction from 13.29 ± 1.21 to 13.00 ± 1.24 years.
Dörte Ostersehlt, Heidi Danker-Hopfe
Abstract
Since there are no recent data on secular changes in growth and maturation of girls from West Germany, two cross-sectional studies with equal design have been carried out in Bremerhaven, North Germany, in 1979/80 and 1989. The present paper presents the results of an analysis of changes in age at menarche based on status quo data from school girls (1979/80: 2,796; 1989: 2,223) aged between 10.0 and 18.5 years. Probit analyses show a reduction over the 10-year period from 13.30 ± 1.19 to 13.01 ± 1.21 years, while logit analyses, which fit the empirical data slightly better, show a reduction from 13.29 ± 1.21 to 13.00 ± 1.24 years.
Croatia Menarche II
Secular growth changes in Zagreb schoolchildren over four decades, 1951–91
Ž. Preberg, V. Jureša, M. Kujundžić
Abstract:
Secular changes in growth and development vary over past decades in intensity and in trend. The purpose of this paper is to present changes in growth patterns of Zagreb schoolchildren aged 7–19 years over the past four decades. Surveys were performed in 1951, 1964, 1973, 1982 and 1991. The mean height of boys and girls in all observed groups has increased significantly over the 40-year period. Age groups up to 9 years in 1991 were 4–7·5 cm taller than their coevals in 1951. Differences increased from the age of 10 in girls and 12 in boys, reaching 10 cm in girls of 12 years and even 14 cm in boys of 14 years. They were also highly pronounced in adult height (5 cm in girls, 7 cm in boys). The most pronounced changes appeared from 1951 to 1964, while in the period from 1964 to 1973 the increase was smaller; in girls only up to 13 years, in to 17 years. However, between 1973 and 1982 positive changes were again significantly pronounced, especially in the older age groups. In the last period, 1982–91, the trend seemed to come to an end. Changes in average weight mostly corresponded to the height changes, being somewhat greater in boys. Moreover, in the last two periods, weight gain in older girls was smaller compared to height. Menarche in the period 1964–73 shifted to a younger age by 8 months (13·34–12·67 years), retaining the same level over the next 9 years. However, since 1982 a slight reverse trend has been noticed.
Ž. Preberg, V. Jureša, M. Kujundžić
Abstract:
Secular changes in growth and development vary over past decades in intensity and in trend. The purpose of this paper is to present changes in growth patterns of Zagreb schoolchildren aged 7–19 years over the past four decades. Surveys were performed in 1951, 1964, 1973, 1982 and 1991. The mean height of boys and girls in all observed groups has increased significantly over the 40-year period. Age groups up to 9 years in 1991 were 4–7·5 cm taller than their coevals in 1951. Differences increased from the age of 10 in girls and 12 in boys, reaching 10 cm in girls of 12 years and even 14 cm in boys of 14 years. They were also highly pronounced in adult height (5 cm in girls, 7 cm in boys). The most pronounced changes appeared from 1951 to 1964, while in the period from 1964 to 1973 the increase was smaller; in girls only up to 13 years, in to 17 years. However, between 1973 and 1982 positive changes were again significantly pronounced, especially in the older age groups. In the last period, 1982–91, the trend seemed to come to an end. Changes in average weight mostly corresponded to the height changes, being somewhat greater in boys. Moreover, in the last two periods, weight gain in older girls was smaller compared to height. Menarche in the period 1964–73 shifted to a younger age by 8 months (13·34–12·67 years), retaining the same level over the next 9 years. However, since 1982 a slight reverse trend has been noticed.
Denmark menarche
A continuous decline in menarcheal age in Denmark
Annette W. Olesen, Bernard Jeune, Jesper L. Boldsen
Abstract:
We report a renewed decline in mean menarcheal age in a large Danish sample after a period with a halt in the trend towards earlier age at menarche in many North European countries. In our study based on retrospective data from six different samples constituting 42784 women, we find a continuously declining mean menarcheal age in Denmark among women born in the years 1964-1973. In a sample of textile workers born in the years 1939-1968 (n = 12605) we find a 1 year higher mean menarcheal age. This indicates that menarcheal age is still delayed in certain groups in Denmark. This leaves the possibility that the menarcheal age could fall even further in the future.
Annette W. Olesen, Bernard Jeune, Jesper L. Boldsen
Abstract:
We report a renewed decline in mean menarcheal age in a large Danish sample after a period with a halt in the trend towards earlier age at menarche in many North European countries. In our study based on retrospective data from six different samples constituting 42784 women, we find a continuously declining mean menarcheal age in Denmark among women born in the years 1964-1973. In a sample of textile workers born in the years 1939-1968 (n = 12605) we find a 1 year higher mean menarcheal age. This indicates that menarcheal age is still delayed in certain groups in Denmark. This leaves the possibility that the menarcheal age could fall even further in the future.
Croatia Menarche
Changes in menarcheal age in girls exposed to war conditions
ivka Prebeg, Irena Brali
Abstract
The purpose of this study was to assess changes in mean menarcheal age of girls in the city of ibenik in the period from mid-1980s to the mid-1990s. ibenik is a Dalmatian town which was exposed to hard war conditions in 1991-1995. Menarcheal status of ibenik girls was surveyed three times, in 1981, 1985, and 1996, and included 720, 1,207, and 1,680 girls, respectively, ages 9.5-16.5 years. Mean menarcheal age was estimated by the status quo method and application of probit analysis. Results show a slight decrease in menarcheal age from 1981 to 1985 (from 12.97 ± 0.06 years to 12.87 ± 0.05), and then a significant increase from 12.87 ± 0.05 years in 1985 to 13.13 ± 0.10 years in 1996. The increase in mean menarcheal age occurred in all socioeconomic groups based on parental occupation and number of siblings. In the group of girls whose homes were damaged during war, menarche occurred at an average of 13.53 ± 0.14 years, while those who lost a family member experienced menarche at an older mean age, 13.76 ± 0.27 years. However, when the girls who experienced personal tragedies were excluded the onset of menarche was still later than in girls surveyed in the earlier periods. The results suggest that the general reversal in the secular trend of menarcheal age in ibenik girls can be attributed to persistent psychological pressures and uncertainties associated with conditions of war. Am. J. Hum. Biol. 12:503-508, 2000.
ivka Prebeg, Irena Brali
Abstract
The purpose of this study was to assess changes in mean menarcheal age of girls in the city of ibenik in the period from mid-1980s to the mid-1990s. ibenik is a Dalmatian town which was exposed to hard war conditions in 1991-1995. Menarcheal status of ibenik girls was surveyed three times, in 1981, 1985, and 1996, and included 720, 1,207, and 1,680 girls, respectively, ages 9.5-16.5 years. Mean menarcheal age was estimated by the status quo method and application of probit analysis. Results show a slight decrease in menarcheal age from 1981 to 1985 (from 12.97 ± 0.06 years to 12.87 ± 0.05), and then a significant increase from 12.87 ± 0.05 years in 1985 to 13.13 ± 0.10 years in 1996. The increase in mean menarcheal age occurred in all socioeconomic groups based on parental occupation and number of siblings. In the group of girls whose homes were damaged during war, menarche occurred at an average of 13.53 ± 0.14 years, while those who lost a family member experienced menarche at an older mean age, 13.76 ± 0.27 years. However, when the girls who experienced personal tragedies were excluded the onset of menarche was still later than in girls surveyed in the earlier periods. The results suggest that the general reversal in the secular trend of menarcheal age in ibenik girls can be attributed to persistent psychological pressures and uncertainties associated with conditions of war. Am. J. Hum. Biol. 12:503-508, 2000.
Belgium Menarche II
"The age at menarche in a national sample of 4894 Flemish schoolgirls
was surveyed in 1979-1980. The probit estimate of the mean age at
menarche was 13.20 +/- 0.02 years (SD = 1.25 years). ... Status quo
secular data for the 20th century indicate a decline in estimated mean
ages at menarche of Flemish girls from about 14.3 years before World
War II to 13.6 and 13.2 years, respectively, among girls born just
before and during the war. Subsequently, mean ages at menarche of
Flemish girls are fairly stable between 13.0 and 13.2 years. These
secular changes are of the same magnitude as those observed in other
European countries."
Wellens, R, Malina, RM, Beunen G, Lefevre J. Age at menarche in
Flemish girls: current status and secular change in the 20th century.
Ann Hum Biol. 1990 Mar-Apr;17(2):145-52.
was surveyed in 1979-1980. The probit estimate of the mean age at
menarche was 13.20 +/- 0.02 years (SD = 1.25 years). ... Status quo
secular data for the 20th century indicate a decline in estimated mean
ages at menarche of Flemish girls from about 14.3 years before World
War II to 13.6 and 13.2 years, respectively, among girls born just
before and during the war. Subsequently, mean ages at menarche of
Flemish girls are fairly stable between 13.0 and 13.2 years. These
secular changes are of the same magnitude as those observed in other
European countries."
Wellens, R, Malina, RM, Beunen G, Lefevre J. Age at menarche in
Flemish girls: current status and secular change in the 20th century.
Ann Hum Biol. 1990 Mar-Apr;17(2):145-52.
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