Primary amenorrhoea: When Periods Fail to Arrive
It is fair that I should start this with a health warning. It is a bit long and an occasional medical jargon could not be avoided. A promise also. It is really accessible and, me thinks, an engrossing read too. Here we go.
From the age of around 11 years, give or take a year or two, girls are expected to start having menstrual periods. It is what is known as menarche. It is a normal life event that marks the start of the reproductive years in the life of the young woman. For most girls that passes off without a hitch. For a few, periods don’t start and for a subset of this group, they never will. We shall get the details shortly. Medically, failure of the periods to start at age 16 in the presence of other pubertal developments (breast development; pubic and armpit hair etc.) is officially abnormal and it is what is termed as ‘Primary amenorrhoea’. If all developments associated with puberty fail to appear, the diagnosis should be made earlier at age 13. Failure to establish menses is a relatively rare occurrence estimated at 0.3% or less than 1 in every 300 women.
What makes periods start
There is a complex interplay of hormones produced in various parts of the body that lead up to onset and monthly occurrence of menstrual periods. The choreography of all these has got to be right for things to happen normally. In addition to the hormones, the anatomy of the lower genital tract has got to be right for the menstrual flow to take place. Sometimes things aren’t as they ought to be and as a result that first period does not materialise. We shall look at some of those causes here. For a logical progression, we shall start from the top (brain) going down.
This is not as difficult as it may first appear so please stay with me. The onset of menstrual of periods is guided by a hormonal pathway that starts from a stimulating hormone that is produced in the part of the brain called the hypothalamus. This stimulating hormone called the GnRH (it is short form for gonadotrophic releasing hormone) stimulates the pituitary gland which in turn stimulates the ovaries to start the process of maturing the eggs and ovulation. In the process the ovaries produce the estrogen and progesterone hormones which act upon the lining of the womb. When pregnancy does not ensue, the lining breaks down causing menstrual bleeding. Still with me? Well, it is that cascade from the hypothalamus, to the pituitary, to the ovaries and finally to the womb that leads to a menstrual period. Now, in some cases, for a variety of reasons the hypothalamus fails to produce the stimulating hormone that ought to launch this process. Periods will not happen.
There are a number of inherited conditions where one of the features is hypothalamic dysfunction and therefore failure of period onset to occur. One of them is called Kallmann syndrome. This condition is a characterised not only by the absence of period onset but also by the absence of development of any of the expected secondary sexual characteristics. There will be no breast development, no axillary (armpit) hair and no pubic hair.
The reason why it is important to make the correct diagnosis early in cases like these is because the absence or severe deficiency of estrogen does not only affect the reproductive system. Other parts of the body that depend on estrogen are adversely affected. Bones come to mind. An undiagnosed and therefore untreated girl with Kallmann Syndrome in her early 20s is likely to be found to have severe osteoporosis usually seen in people in their 70s or older.
Following a diagnosis of Kallmann Syndrome, the affected girl will be put on hormone therapy and this is continued for life. The descriptive medical term for Kallmann syndrome is ‘hypogonadotropic hypogonadism’
Pituitary gland dysfunction
Problem affecting the pituitary gland can start before puberty even though this is rare. When it happens, periods may fail to start when expected. A prolactinoma is a benign tumour that produces excessive amounts of prolactin hormone. This hormone is normally responsible for milk production. The majority of prolactinomas are tiny in size, hardly ever larger than one centimetre in diameter and surgery is very rarely required.
Radiotherapy to the brain in childhood can lead to functional failure of the pituitary gland. This can also occur as a result of head injury if the pituitary gland sustains significant trauma. This will lead to failure of the gland to produce the hormones that stimulate the ovaries.
Polycystic Ovarian Syndrome (PCOS)
Even though polycystic ovarian syndrome is mainly associated with secondary amenorrhoea, it can also cause primary amenorrhoea. If the girl affected by this condition is overweight, she may reach the critical age of 16 before her first period has appeared. She will have developed the other secondary sexual characteristics. In fact the hair distribution may give the first clue as to the possible diagnosis as pubic hair tends to extend higher onto the abdomen. A hormone profile blood test and pelvic ultrasound scan will tend to clinch the diagnosis.
Premature ovarian failure
1 in 10,000 girls will suffer from premature ovarian failure before the age of 20. In rare cases, this occurs before the girl has had her first period. In effect, ovaries lose their function and the girl is effectively in a menopausal state. Making a timely diagnosis is vital to avert the consequences of long term estrogen deficiency, most notably osteoporosis. Long term estrogen replacement, at least until the age of 50, will be required.
Chromosomal and genetic disorders
Girls with this syndrome, named after the two Swiss paediatricians (Andrea Prader and Heinrich Willi) who first described it present with, among other features, primary amenorrhoea. The underlying problem is a defect in Chromosome No.15. Remember there are 23 pairs of chromosomes. Other notable features include short stature, increased appetite which leads to obesity and learning difficulties.
This is a chromosomal disorder that is uncommon but not rare. Instead of having two X chromosomes, these girls have only one. Normal chromosomal make up is represented as 46XX. In Turner’s syndrome it is represented as 45X0. This is descriptive as it shows that these girls have 45 chromosomes (instead of the usual 46) and the ‘0’ represents the missing X chromosome. The problem here is that the ovaries lose their germ cells which are responsible for the production of estrogen and progesterone hormones. The ovaries are therefore non-functional.
46XY gonadal dysgenesis
Girls with this condition are actually genetically male. Their chromosomal make up is 46XY as shown in the name. Something fundamental goes seriously wrong at the fetal stage. A gene on the Y chromosome (the ‘male’ chromosome) undergoes mutation. As a result of that mutation, testes cannot develop. In addition, a vital hormone called the ‘antimüllerian hormone’ is not produced. The result of all this is that the fetus reverts to the default position which is to develop female genitalia. The baby is born with a vagina, uterus and fallopian tubes. Crucially, there are no functioning ovaries. As a result, periods will never start and it is usually at this stage of life that the diagnosis will be made.
Another form of gonadal agenesis is where the girl is actually genetically and constitutionally female (46XX) but where the ovaries are not functional. The secondary sexual characteristics do not develop and, of course, periods do not start. This is 46XX gonadal dysgenesis
Anatomical abnormalities of the genital tract
Sometimes all the hormonal systems are working as they should but abnormalities in the lower genital tract mean no menstrual flow is possible. These abnormalities could take the form of an absent or poorly developed uterus, an absent or blocked vagina or a hymen that is completely closing off the vaginal opening.
There is a specific syndrome whereby the uterus and the upper two third of the vagina is missing. The external genitalia and lower third of the vagina are normal. It is therefore difficult if not impossible to suspect anything amiss before the early teens when failure to start menstruating could lead to tests and diagnosis. Occasionally, these girls are found to have renal (kidney) abnormalities as well. Secondary sexual characteristics develop normally. This condition is not that rare, affecting 1 in every 4500 girls. If you want to know the scientific name, it is Mayer-Rokitansky- Küster -Hauser syndrome
As the name suggests, this is a condition where the hymen is completely covering the vaginal opening. Everything else in the genital tract is normal. These girls will start menstruating normally but the blood will be retained in the genital tract as it has no way of escape. After a few months of this, the girl may report cyclical lower abdominal pain coinciding with the time when she is supposed to be having a period. Examination will easily establish the diagnosis and a simple surgical procedure to open the hymen will allow the accumulated blood to escape. Periods will continue normally thereafter.
This list is by no means exhaustive. Even though primary amenorrhoea is not as common as secondary amenorrhoea (where periods start normally then cease, temporarily or permanently), the list of potential causes is much longer. It is important to mention here that in the majority of cases where there is apparent delay in starting a period, there is actually nothing wrong. This is what is termed as ‘constitutional delay’. If other secondary sexual characteristics have developed normally, it is perfectly reasonable to wait until the 16th birthday before seeking medical help. After this point, a doctor’s attention is advisable. Even at this point, many will be found to have no serious underlying problem but delaying seeking help beyond this point is not advised.
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