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Infertility and missed periods

Infertile women may miss their periods. This is called amenorrhea; and because there are many possible reasons for this, it's important to perform medical tests to find the right diagnosis, so it can be treated correctly

Missing a period can be very difficult for infertile women! Every time you miss a period, you hope ( against hope) that maybe you are finally pregnant! However, you are worried about getting your hopes up too high, because you are scared that they will come dashing down again - and you remember all the false alarms you have had in the past!

There are many reasons for missing a period, including stress; side effects of medications you are taking; and a systemic illness. The first step, of course, is to rule out a pregnancy. You can do this by checking with a urine pregnancy test kit. The new ones are very reliable, and a negative test result usually means that you are not pregnant. If you are unsure, you can repeat the test in 2 days. A better option is to do a blood test to check your HCG level. This is much more reliable ( but it's also much more expensive!). A blood level of less than 10 mIU/ml confirms you are not pregnant.

If you miss three menstrual periods in a row, your doctor will make the diagnosis of secondary amenorrhea . This is just medical jargon for - has missed more than three menstrual periods. It's not really a diagnosis - just a description of your problem.

So what are the reasons for a missed period ? And what can you do about this ?

Let's start with the basics. In order to get a period, you basically need just two things:

1. a uterus, which sheds its uterine lining as a period
2. hormones ( estrogen and progesterone) which act on the uterine lining, and cause it to shed

If you miss a period, this means there are only 2 broad possibilities.

1. There's a problem with the uterus. Thus, is may be damaged ( because of intrauterine adhesions)

2. There's a problem with the reproductive hormones . Their levels may be too low; or too high; or out of balance !

The first test the doctor may do is a vaginal ultrasound scan to check your uterus; and your uterine lining. If this is normal, then it's likely the problem is with your hormones.

Sometimes, the doctor may give you hormones as a therapeutic trial to see if this can induce your period. This is called a progesterone challenge test; and consists of 5 days of 20 mg medroxyprogesterone daily. Thus, if you get your periods after taking progesterone, this means your uterus is fine; that you have high estrogen levels; and that you are not producing progesterone on your own ( this is the picture classically found in women with PCOD).

If you do not get your periods after taking the progesterone, this means either that your uterus is damaged; or that you are not producing enough estrogen. The other possibilities include: pregnancy; and the possibility of a functional ovarian cyst ( which can produce estrogen and progesterone and delay the period)

The commonest cause for a missed period in infertile women is anovulation. Let's review some more basic biology . The reason women who ovulate get a natural menstrual period is because of a drop in the circulating blood levels of the reproductive hormones, estrogen and progesterone hormones. When these levels drop, the uterine lining loses its hormonal support, as a result of which it is shed as a menstrual period. This is called a estrogen primed progesterone withdrawal bleed.

A missed period means there is a problem with the normal balance between estrogen and progesterone in your body. This usually happens when you do not ovulate. This is called anovulation.

Most women ( for example, those with PCOD) have high estrogen levels, but because you have not ovulated, your progesterone levels remain low, as a result of which you do not get a withdrawal bleed.

In other cases, the corpus luteum forms a functional cyst. Because this continues to produce estrogen and progesterone, there is no progesterone withdrawal, and the lining remains thick and does not shed.

Others have low estrogen levels ( as a result of which your uterine lining remains thin and does not develop at all). This is commonly seen in lean athletic women who exercise a lot. The missed period in these women is called hypothalamic amenorrhea.

In order to come to the right diagnosis, the doctor may need to do a vaginal ultrasound scan .

This should check for the following.

  1. Is there a cyst in the ovaries ? Are the ovaries small ? What's their volume ? The antral follicle count ?
  2. The endometrial thickness and texture.

Patients with PCOD will have a thick uterine lining, which suggests they have high estrogen levels. Women with hypothalamic amenorrhea have small ovaries with a thin lining; as do perimenopausal women who have reached the oopause and whose ovaries are failing. A functional cyst will be easily apparent on the scan.

It's also possible to confirm this diagnosis by checking the blood levels of estrogen and progesterone.

After making a diagnosis, it's easy to induce a period, based on the problem.

If the uterine lining ( endometrium) is thick, this means that the level of estrogen in the body is already high; and it's easy to induce a period by taking 5 days of progestins, such as medroxyprogesterone acetate. There are many options available. These include:Tab Provera ( medroxyprogesterone acetate), 10 mg, twice a day. The period will usually start 3-7 days after taking the last tablet. This is called inducing a withdrawal bleed with progestins.

On the other hand, in women with low estrogen levels who have a thin uterine lining, we first need to build up the lining with estrogens and then induce a period with progesterone . We give the estrogen and progesterone hormones sequentially, thus mimicking a natural cycle. This is what a typical prescription would look like.

Estrogen tablets from Day 1 - Day 25. There are many options available. The least expensive is Tab Ethinyl estradiol ( Lynoral), 0.05 mg daily. Other choices include:

  • Tab Premarin, 1.25 mg daily; or
  • Tab Progynova ( estradiol valerate, 2 mg), 2 tab daily. You may feel some nausea and have some temporary fluid retention while taking the estrogen.

Progestin tablets, from Day 16 - Day 25. There are many options available. These include:Tab Provera ( medroxyprogesterone acetate), 10 mg, twice a day.

This regimen is called Hormone Replacement Therapy, and is available commercially in some countries in the form of a pack, called CycloProgynova.

The withdrawal period ( menstrual period) will start approximately 3-6 days after you take the last tablet, as the levels of the administered hormones decline in your body because they get excreted in the urine.

It's also possible to achieve the same results with a 21 day course of birth control pills, since these contain both estrogen and progesterone. It's best to take the old-fashioned monophasic birth control pills, which contain a sufficient amount of estrogen and progestins ( combined together in one active tablet). A typical choice would be Ovral, which contains 50 ug of ethinyl estradiol and 500 ug of norgestrel ( a type of progestin). The withdrawal bleeding induced when you take birth control pills may be scanty as compared to a regular period. This is normal.

If the reason for the missed period is a functional cyst, you may have to wait till it resolves. It will usually do so on its own. If needed, the doctor can induce a period with mifegest ( RU-486), a very powerful antiprogestin.

Authored by : Dr Aniruddha Malpani, MD and reviewed by Dr Anjali Malpani.