Menarche ≤11 years and Nulliparity is a risk factor for Premature and Early Menopause.

courtesy: youtube.com

Women who had their first period at or before the age of 11 are at increased risk for premature and early menopause and the risk is further amplified if the woman is nulliparous according to a large observational study published on January 25, 2017 in Oxford Journal of Human Reproduction.

It is already known that premature menopause and early menopause are at high risk for CHD, CVD and all-cause mortality. These women can be benefited by pharmacological and life style interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.[1]

This was a pooled analysis of data of 51,450 postmenopausal women from observational studies that contributed to The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project.[2]

InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies.

Age at menarche was categorized into ≤11, 12, 13, 14 or more years and parity as nulliparous, 1 or 2 children. Premature Menopause is defined as Final Menstrual Period (FMP) before the age of 40 years and Early menopause is when FMP is between 40–44 years.

After multivariate regression analysis, it was seen that:

Median age at menopause was 50 years. About 2% of women had early menopause and nearly 8% women had premature menopause.

Women with first period at ≤11 years of age were 1.39 times the risk early menopause, 1.8 times the risk of premature menopause as compared to women who had first period after ≥12 years of age of age.  

Nulliparous women were at 1.32 times the risk of early menopause 2.26 times the risk of premature menopause.

Women who were nulliparous and had menarche at ≤11 years of age were 2 times the risk for early menopause and 5 times the risk for premature menopause as compared to those who had menarche ≥12 years and had one or more children.

The study supports the finding that women at risk of premature/early menopause can be identified  by history and can be  benefited by pharmacological and lifestyle interventions to prevent the increased all-cause mortality and CVD risk they are put at due to accelerated reproductive aging.

Complex relationship exists between cardiovascular health and accelerated reproductive aging and further research is needed to clarify the issue.

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[1] https://obgynupdated.blogspot.com/2016/09/premature-or-early-onset-menopause-is.html

[2] https://www.ncbi.nlm.nih.gov/pubmed/27621257

Late Menarche, Late Menopause and Longer Reproductive lifespan linked to increased longevity.

Clinical Pearls:

• Women who had menarche at age 12 or more and experienced menopause at age 50 or beyond have increased odds of living up to age 90 as compared to women who have early menarche and early menopause.
• Those women whose reproductive life span lasted 40 years, were 13% more likely to celebrate 90 birthdays than women who were in reproductive period for 33 years. (odds ratio [OR]= 1.13).

A new study by researchers at University of California, San Diego found an interesting correlation between the age at menarche and menopause and longevity. Women who enter the reproductive period late and also have a late menopause are more likely to live till age 90.

The research implicated that women who had menarche at age 12 or more and experienced menopause at age 50 or beyond have increased odds of living up to age 90. 

According to Dr Aladdin Shadyab, of the University of California, San Diego School of Medicine "People have always wondered whether the timing of reproductive events affect longevity, but no study to date has evaluated that relationship."

The study was published in recent issue of Menopause, the journal of North American Menopause Society. [1]

The research team used data for Women’s Health Initiative study (WHI). The Women's Health Initiative (WHI) is a long-term national health study that recruited women from 1993 to 1998 and followed them until 2014 focusing on strategies for preventing chronic health diseases in postmenopausal women. This multi-million dollar, ground-breaking study has far reaching implications and have provided the health care providers with practical information to prevent and treat some of the major diseases impacting postmenopausal women. [2]

The study participants included 16,251 women from diverse racial and ethnic background all born before August, 1924. Multivariable logistic regression models were used to determine the association, adjustments were made of demographics, reproductive history and lifestyle of the women.

The average age of the study participants was 74. 7 years and 8,892 (55%) of the women lived through age 90.

As compared to those women who had an early menarche before age 12, those women who were at-least 12 or older at menarche have a 9% increased chances of living upto age 90. (odds ratio [OR]= 1.09).

Similarly, women who were at least 50 at the time of last period are 20% more likely to live till 90, as compared to women who stopped menstruating before age 50. The same was true for women who underwent surgical menopause. (odds ratio [OR]= 1.19).

Longevity was also tied to a longer reproductive life span. Those women whose reproductive life span lasted 40 years, were 13% more likely to celebrate 90 birthdays than women who were in reproductive period for 33 years. (odds ratio [OR]= 1.13).

The authors of the study cannot pinpoint a single reason behind this association, but multiple factors come into play.

Early menarche is often associated with obesity, Diabetes and CVD while early menopause is also linked to increased risk of CVD. These associated co-morbidities in women experiencing early menopause may be responsible for shorter life span.

Genome-wide association study of age at natural menopause identified genetic variants involved in DNA replication and repair pathways which is crucial in aging. Thus genetics is also an important factor.

The study has limitations of not knowing the longevity of the parents and other family members of the participants along with the work history and stress, which plays an important role in deciding longevity.

One other study published this week in Proceedings of the National Academy of Sciences and Biological Psychiatry, has shown that women with early menopause suffer from insomnia which accelerates aging and shortening the life span.[3]

The last decade has seen rapid improvement in life expectancy of older women adding average of 7 years to their life expectancy as compared to men[4] with a current total population of 1.3million women over the age of 90+.  Women surviving into their 90s outnumber men by a ratio of almost three to one.[5]

The authors conclude "With secular trends showing decreasing age at menarche, increasing age at menopause, and a concurrent rise in longevity, additional studies in younger birth cohorts will be needed in the future to precisely define the relationship between the timing of reproductive events and a woman's length of life."

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[1]http://journals.lww.com/menopausejournal/Abstract/publishahead/Ages_at_menarche_and_menopause_and_reproductive.97952.aspx

[2] https://www.whi.org/about/SitePages/About%20WHI.aspx

[3] http://newsroom.ucla.edu/releases/menopause-sleepless-nights-may-make-women-age-faster

[4] http://www.census.gov/prod/2011pubs/acs-17.pdf

[5] https://www.census.gov/newsroom/releases/archives/aging_population/cb11-194.html

The New Puberty

The New Puberty

The Book" The new puberty"

This article is based on TEDMED talk 2015 in Palm Springs, California by Pediatric endocrinologist Louise Greenspan and her groundbreaking book, -“The New Puberty: How To Navigate Early Development in Today’s Girls”, along with coauthor Julianna Deardorff, a Berkeley professor of Maternal and Child Health and adolescent psychologist.

Just a generation ago, fewer than 5 percent of girls started puberty before the age of 8, today girls are entering puberty at increasingly younger ages with 10% of girls now showing the first signs of puberty before age 8.

Early puberty can lead to eating disorders, depression, substance abuse, early sexual activity and, later in life, breast cancer.

According to Dr. Greenspan, two important culprits responsible are obesity and family stress.

"We used to say that breast development and pubic hair should not start before age 8. What we know now is that 15% of girls at age 7 are showing breast development," Dr Greenspan reported.

According to Biro.F.M  et al in Pediatrics 2013;132:1019-1027 Girls from racial and ethnic groups with the highest rates of obesity are most at risk for early puberty. In that study, black girls showed breast budding at an average age of 8.75 years, Hispanic girls at an average age of 9.25 years, and white and Asian girls at an average age of 9.75 years.

Higher BMI was the strongest predictor of earlier age at breast stage 2 in this study

The relationship between higher BMI and earlier onset of puberty in girls has been noted previously; in 2 large cross-sectional studies, Pediatric Research in Office Settings (PROS) and the National Health and Nutrition Examination Survey (NHANES) III, earlier maturation occurred in those girls with greater BMI and in those with BMI ≥85th percentile.

Body fat makes estrogens, which are the same kind of hormone that are normally released from the ovaries during puberty. When there is more body fat, there are higher levels of estrogen, which leads to breast budding.

In USA the rate of obesity in children aged 6 to 11 years of age increased from 7% in 1980 to nearly 18% in 2012, according to a report from the Centers for Disease Control and Prevention.

And during the same period, the rate of adolescents 12 to 19 years of age who were obese increased from 5% to nearly 21%.

The trend is not just seen in the U.S., it's seen in multiple countries, probably more so countries closer to the equator than countries in the northern latitudes. But major factor is likely to be, certainly in the developing countries, a switch from a more traditional diet to a more Western diet, which results in greater, perhaps better nutrition or perhaps over-nutrition, and that's certainly a factor.

Stress is the second important factor in causing early puberty; other risk factors are early sexual abuse and toxic levels of family arguments and neighborhood violence.

Dr Greenspan says that “Most notably, a girl who grows up without her biological father is twice as likely to get her period before age 12 as a girl who lives with her biological father.”

She does not refute the endocrine-disrupting chemicals commonly found in plastics and pesticides for early puberty, but it is almost impossible to eliminate endocrine-disrupting chemicals from our environment, and there is no single smoking gun, she explained.

These chemicals can mimic hormones in the body, and some mimic hormones that are important regulators of puberty, particularly estrogen. However, more research is needed on humans.

She noted that "a much more effective public health intervention would be to try to tame the obesity epidemic and put some greater social infrastructure in place to buffer children from the stresses of poverty."

The authors offer highly practical strategies that can help prevent and manage early puberty including limiting exposure to certain ingredients in personal care and household products, which foods to eat and which to avoid, and ways to improve a child’s sleep routine to promote healthy biology.

Moreover, the authors—both mothers of young girls—offer parents, teachers, coaches, and caretakers guidance to initiate and continue the conversation about puberty in an age-appropriate way to support girls as they navigate this complex stage of their lives.

References:

http://thedianerehmshow.org/shows/2015-05-06/whats-behind-early-puberty-in-girls

http://www.jpagonline.org/article/S1083-3188%2812%2900092-7/abstract?cc=y

http://pediatrics.aappublications.org/content/132/6/1019.long

http://www.nytimes.com/2015/02/05/opinion/what-causes-girls-to-enter-puberty-early.html?_r=0

Rosenfield RL, Lipton RB, Drum ML. Thelarche, Pubarche, and Menarche Attainment in Children With Normal and Elevated Body Mass Index. PEDIATRICS 2009;123(1): 84–88

http://pediatrics.aappublications.org/content/132/6/1019.long#xref-ref-4-1