A series of genetic signals that influence the age females begin menopause has been found, which would help infertility treatment that could extend the natural reproductive lifespan of women. Menopause means the end of menstrual cycles in women. After a woman goes twelve months without a menstrual period, it is disorganized. Menopause happens in the 40s and 50s, and the average in the US for menopause is 51. It is a natural biological process but comes with physical symptoms, including hot flashes, emotional health, sleep disturbance, and lower energy level. There are many effective treatments like hormone therapy and lifestyle changes.
Research in detail –
The researchers scanned the genes of more than 200,000 women. They found three hundred genetic signals that could help determine why some women get early menopause, what health consequences one has to face for early menopause, and improve fertility if these signals can be manipulated.
The scientists from Copenhagen, Exeter, Cambridge carried the study and are still in their early stages. They found that CHEK1 and CHEK2 were the main genes in understanding the difference between these women. When CHECK2 inhibited mice, a longer reproductive life span was found in their offspring. Similarly, in the mice when CHEK1 was overexpressed, the offspring’s reproductive life span was extended by increasing the starting number of eggs in fetal life.
According to their data, women who do not have enough CHEK2 protein experience menopause three years later than those with normal CHEK2 levels. Certain health impacts were also examined by the researchers of having late or early menopause. They found genetically, early menopause was associated with poor bone health and a high risk of fractures, and an increased risk of type 2 diabetes. Earlier in menopause, the risk of some type of cancer is reduced, like ovarian and breast cancer.
Study co-author Dr. Katherine Ruth of the University of Exeter said: “We found that earlier menopause was causally associated with a lower risk of hormone-sensitive cancers. We think this is probably due to having a shorter lifetime exposure to high levels of sex hormones (which are at higher levels while a woman is still menstruating).” She also hopes that their work will help to plan new possibilities to help women plan for the future. In the timing of menopause, by finding many more of the genetic causes of variability, they have shown that they can start to predict which women menopause will be early and will have to face getting pregnant naturally. And because women are born with their genetic variations, they can offer this advice to young women.
From the University of Copenhagen, Prof Eva Hoffmann, also a co-author of the study, said that their findings offer potential new therapeutic approaches that might help treat infertility, particularly in IVF treatment. She further said several safety concerns and scientific questions have to be considered before human trials are done. But their study shows that IVF treatment that targeted short-term inhibition of these pathways could help some women respond better.
The reproductive life span in women begins with puberty and ends with menopause. The timings of menopause vary considerably among women. Between the age of 40 and 60, most women go through menopause. About 1% have their menopause before 40. To every health condition, this timing is determined by genetics along with lifestyle and environmental factors.
Environmental factors such as BMI and smoking are well studied, but the genetic basis of menopause has been very limited. These genetics concepts have been difficult to investigate. A woman’s egg supply is determined before birth in the womb during her reproductive lifespan, triggered by DNA damage some are lost due to cell death. According to the University of Cambridge study author Dr. John Perry, they found five times as many genetic factors as were known earlier. In terms of what is known about the genetics of menopause, it is a huge finding.
The main aim of the study is to help to predict a female natural fertility window. Some tests are done to measure hormones that indicate that females have a low ovarian reserve. But by the time it is detected, the decline has already begun. When the decline begins, there is no long-term predictor. Further research could help identify some females at higher risks compared to others said, Perry.
According to Perry, they are working towards this sort of predictive test where someone’s DNA could be analyzed and then try to interface with their natural fertility window. This will help women to make more informed reproductive choices.
Based on identified genetic variants, the researchers also drafted a risk score to assess whether it is possible to determine which women would reach early menopause. The predictive ability of genetic risks against the best non-genetic predictor they knew of was compared by the researchers, which was smoking. For clinal utility, their genetic score has reached up to that level.
Earlier researches are done on menopause –
Genome-wide association study (GWAS) has come into use to overcome the limitations of candidate gene association approaches and genome-wide linkage analyses to discover susceptibility loci for early menopause.
Early menopause is a heterogeneous and complex disorder influenced by many environmental and genetic factors and interactions between these factors. Early menopause is marked by estrogen deficiency, increased gonadotrophin levels, amenorrhea, and can be spontaneous or induced. Induced early menopause can be caused to due medical interventions such as surgery or chemo for cancer. While spontaneous and early menopause can be caused by can result from a wide range of causes such as autoimmune disorders, enzyme deficiencies, or metabolic syndromes, inflammatory conditions or infections, genetic abnormalities, or mutations. At the same time, many studies have used GWAS to identify genetic loci associated with the onset of menopause.
To research candidates with early menopause, the following strategies were used –
- T For the genetic study of early menopause, the PubMed database was searched from inception to 2018. They used “early menopause” and/or “natural menopause” as keywords.
- Only studies on mice or humans were included.
- Subjects from different ethnicities were included in the study.
- Then the study included a reference list that was scanned to identify other potentially useful studies.
Females are born with one million primordial follicles and began with about 500,000 in the first occurrence of menstruation. By the age of 40, only a few thousand remain. Three methods were used for this GWAS, candidate gene association, genome-wide linkage analysis.
At the onset of natural menopause in genome-wide linkage analysis, it was found the age has found the involvement of one strong candidate locus, Xp21.3. Few suggest the involvement of loci 11q23.3, 16p13.3, 8p22, and 9p21.3. However, these results have not been repeated and need further verifications.
In the candidate gene association approach, the molecular basis of early menopause is investigated. Based on educated guesses of the associated pathways, the candidate’s causative genes are selected. MCM8 and MCM9, in a few POF pedigrees which are mutated, are potential genes responsible for early menopause. This research is limited because of incomplete knowledge of the human genome, and important pathways and genes can be overlooked.
GWAS has been used recently to overcome the limitations of the candidate gene association approach and genome-wide linkage analysis in finding out susceptibility loci for early menopause. The study found out that the age of the first occurrence of menstruation and age at natural menopause is associated with causes of substantial mortality and morbidity such as cardiovascular disease and breast cancer. Thirteen associated SNPs were identified for age at early menopause clustered at 20p12.3, 19q13.42, 5q35.2, 6p24.2.