The secret history of the menopause

The menopause, which simply means stopping menstruation, marks the end of a woman’s reproductive life. In fact, it is a universal feature of all mammalian females. Why is there a menopause? Some people believe that the menopause frees older women from hormonal upset and childrearing, so they can pitch in and look after the grandchildren. Others argue that it is simply set by how long a species needs to raise infants to the age of independence, or to avoid the increased dangers of childbirth in middle age.

On a basic biological level, to understand exactly why it happens when it does, we need to go right back to the beginning, before birth.

From the moment of conception, chromosomes define a baby’s gender.  An X and a Y chromosome mean a boy. Two Xs mean a girl. At around four months in the womb, a female foetus already around seven to 20 million primitive eggs in her ovaries. This is the most eggs a female will ever have, right now when she is completely unable to use them. Each tiny egg becomes embedded into a special follicle, which is a fluid-filled cavity on the ovary. While these follicles are forming, most of the eggs gradually waste away.

By the time a girl baby is born, she has around two million eggs left, and no more develop after birth. When she reaches puberty, she will be lucky to have 400,000 remaining due to factors like childhood illness, accidents, even environmental pollution. Each time she has a period, one egg (or sometimes two) is released, but that’s not the end of the story. Thousands of eggs continue to die every month, but there are still plenty left to last for decades. When there are around 25,000 eggs left, usually at age 37, this process of elimination speeds up until the numbers are down to around 1000 eggs remaining in a peri-menopausal woman aged around 45.

In the normal course of events, monthly bleeding, or menstruation, happens regularly, unless a woman becomes pregnant and the cycle temporarily stops. Everything runs smoothly because the body has an inbuilt biological clock, which is governed by fluctuating levels of hormones. Controlling all, is the pituitary gland, a pea-sized gland located directly behind the hypothalamus. The pituitary gland releases hormones including luteinizing hormone and follicle-stimulating hormone. These, in turn, stimulate the reproductive glands in turn to release sex hormones, oestrogen and testosterone.

Here is a simple overview of what happens during a woman’s menstrual cycle, which lasts an average of 28 days.

Follicular phase: DAY 1-13

On the first day of a woman’s period, low levels of oestrodiol, an oestrogen, and progesterone cause the womb lining to degenerate and to be shed. Levels of the follicle-stimulating hormone rise slightly, which stimulates the development of several follicles, each containing an egg. Usually, only one follicle continues to develop. During the last stage of this phase, the ovaries begin to secrete more oestrodiol, which cause the uterine lining to start to thicken.

Ovulatory Phase: DAY 13-15

The pituitary gland releases a surge of luteinizing and follicle-stimulating hormone. Around 24 hours later, ovulation takes place when the egg is released from the follicle. Some women report feeling a dull pain on one side or the other when they ovulate. This is known as mittelschmerz, and can last from between a few minutes to a few hours. Now progesterone levels begin to fall.

Luteal Phase: DAY 15-28

Now, levels of both luteinizing and follicle-stimulating hormone are falling. The ruptured follicle, now changed into the corpus luteum, produces progesterone, which causes the womb lining to begin to thicken in preparation for pregnancy. If the egg is not fertilised during its passage down the fallopian tube, the corpus luteum breaks down and stops producing progesterone, which is the hormone that protects pregnancy. Oestrodiol levels slowly start to creep back up which causes a new menstrual cycle to begin.

It is worth bearing in mind that 28 days is just the average length of a menstrual cycle. In fact, menstrual cycles range from between 21 to 35 days. Only 10-15 per cent of cycles are exactly 28 days.

By the beginning of a woman’s fourth decade, hormone activity is beginning to change. This is the onset of the menopause.

Peri-menopause, which is the period leading up to the menopause proper, begins to make itself felt at around the age of 45. It comes with all kinds of tell-tale signs, more of later. The average age for the menopause, which is confirmed when you have no periods for 12 months in a row, is now 51. The next five years involve the hormones readjusting.

So what’s going on during the peri-menopause?

Levels of oestrogen and progesterone both decline as stocks of  eggs begin to run low. In particular, the follicular phase of the menstrual cycle begins to shorten. Periods may start to vary in duration and flow may become lighter, or heavier. The ovaries become less responsive to the hormones secreted by the pituitary gland, so they, in turn, secrete smaller amounts of the sex hormones. Egg release gradually stops altogether.

Interestingly, studies show that the average age at which this happens is later than it used to be. There are various theories about the reasons why, but most experts link it to better nutrition and general health. For the same reasons, puberty is beginning earlier too. The average age at which a girl has her first period decreased by four months for each decade between 1850 and 1950, although it has only made small downward adjustments since then.

The timing of the menopause is down to a great many contributing factors, perhaps even the time of year that a girl was born. Research by Italian experts has found that the timing of the menopause can be determined by the month of birth. They found that Spring babies tend to reach their menopause earlier than those born in the Autumn. The study, which involved nearly 3,000 women and conducted in four university hospitals in central Italy (Bologna, Ferrara, Medina, and Parma), was published in Europe’s leading reproductive journal, Human Reproduction. The author, Dr Angelo Cagnacci, said that the data suggested a role for environmental factors in regulating adult reproductive life. Whether this is due to temperature and sunlight, or seasonally linked dietary modifications or even exposure to infection, no one can say for sure. Dr Cagnacci theorises that early mortality is highest among children born in Autumn. Thus, the survivors are a tough breed and pass their hardiness on to their offspring.

Of course, early menopause can also be due to environmental factors, and lifestyle choices. Scientists from Massachusetts General Hospital, publishing in the magazine Nature Genetics, have discovered that women, who smoke, expose the eggs in their ovaries to chemicals, which kill them off. Cigarette smoke-derived chemicals, called polycyclic aromatic hydrocarbons, travel through the bloodstream and enter the egg cells, attacking them from within – literally causing them to commit suicide.

The egg undergoes its programmed cell death, but much earlier than it should have done. The scientists confirmed their findings using human ovarian tissue grafted under the skin of laboratory mice.

Autoimmune disorders may hasten its onset, and artificial menopause can be induced by surgical removal of the ovaries, or chemotherapy or radiation treatment for cancer.

Genetics may be the biggest single thing that determines the timing of the menopause. Mothers and daughters may get the menopause around the same age. Research published in the Journal Human Reproduction found that menopause is 85 per cent genetically determined. The Dutch research team collected data from 243 non-twin sisters, 22 non-identical and 37 identical twins. For non-twin sisters, the age at which they reached the menopause was 85-87 per cent down to genetic factors. For twins, it was 70 per cent. Dr Jan-Peter de Bruin, who headed up the research team at the University Medical Centre in Utrecht, said: “A woman with one or more first-degree relatives with a history of early menopause is liable to experience earlier menopause herself.”