And It's About Time There Was Some Support For Cushing's!
From The Fertility Sourcebook, Sara Rosenthal, M. Rosenthal, Masood A. Khatamee, M. S. Rosenthal MS, Masood A. Khatamee MD
By M. Rosenthal
If your ultrasound results are normal, you'll begin a series of hormone tests that will be taken at different times in your cycle. The process begins by discussing your menstrual charts with your doctor, who may have observed some unusual patterns in the cycle right off the bat. For example, some BBT charts have flat patterns, whereas others have too many peaks and valleys.
Again, roughly 30% of all female infertility is caused by a hormonal imbalance of some sort. Depending on what kind of imbalance you have, you'll be plagued with different symptoms that include irregular cycles, failure of the embryo to implant in the uterus, poor-quality cervical mucus, or the inability to sustain a pregnancy, causing you to repeatedly miscarry. Some ovulatory problems are not obvious. For example, even though you may not be ovulating every month, you could still have regular periods. This is known as an anovulatory cycle.
When irregular ovulation is cited as the probable culprit, you'll undergo a series of simple blood tests done at various points in your cycle (different hormones peak at different times) to find what hormone is either missing, deficient, or exploding from your body. Assuming a 28-day cycle, on day 2 or 3 of your cycle, FSH, LH, and estradiol (a type of estrogen) are measured. Then, during the luteal phase (anywhere from days 22-24), progesterone levels are measured. Your doctor will check your levels of gonadotropin-releasing hormone (GnRH) and androgen levels. Prolactin levels can be checked at any time during your cycle, but it's best to do it in the morning, and for you to avoid touching your breast prior to the test. Touching your nipples or breasts, for example, may stimulate the hormone, and throw off the test, causing inaccurate results. You'll most likely undergo an(other) transvaginal ultrasound and endometrial biopsy (see further below) to accompany some of these blood tests.
This is an important test for women who have either bouts of amenorrhea (no periods) or chronic amenorrhea. This test determines whether the amenorrhea is caused by a uterine abnormality or a hormonal imbalance. Is the uterine lining getting thick enough to shed to begin with? If it isn't, you don't have the right amounts or combinations of hormones in your body to trigger a period. Is your uterus thickening each month but somehow not responding to your hormones, which is a signal to shed? There's an easy way to find out. Progesterone is given to you either orally or by injection to induce a period or "withdrawal bleeding." If the bleeding starts, then the problem is clearly a hormonal one. The hormonal problem will then need to be pinpointed by further tests. If you still do not bleed despite hormonal supplements there's either a uterine abnormality at work that will need to be ruled out, or you may not have enough estrogen to respond to the progesterone withdrawl.
During your initial physical exam, your doctor will be checking to see if you have body hair on your breasts, back, abdomen, face, and so on. Your doctor may not notice that you have excessive hair because you might be removing it. If you're asked this question, you should answer truthfully.
There is a condition known as polycystic ovarian (PCO) syndrome. This is a condition where your ovaries have small cysts that interfere with ovulation and hormone production. You'll also be asked about any skin problems such as acne, and you may also have a history of irregular periods and/or a battle with obesity. Obesity, oily skin and acne, irregular cycles, infertility, and excessive hair growth are symptoms of PCO.
If you have this problem, you're probably not ovulating regularly, which will show up in your menstrual charting. Your doctor will do some additional blood tests in this case to check for any elevated levels of androgen, a male hormone all women secrete in small amounts. You can also have elevated androgen levels and not have PCO. If androgen is the problem, you may need to be put on female hormone supplements such as estrogen replacement to offset it. PCO is treated with fertility drugs and is a classic, "textbook" cause of female infertility.
There is a genetic condition known as Turner's syndrome, which affects roughly 1 in 2,500 women. Turner's women have either a missing or a damaged X chromosome (normally, women have two X chromosomes). These women are short, not growing beyond about 4 feet 7 inches, and usually have other medical problems, including ear, eye, heart, kidney, or thyroid disorders, diabetes, high blood pressure, and keloid healing.
These women also lack many secondary sexual characteristics (such as breasts or pubic hair), have irregular or nonexistent menstrual cycles, and are usually infertile. Other physical features include low-set ears, a low hairline, a webbed neck, pigmented moles, bending out of the elbows, and puffy hands and feet. Finally, while Turner's women are not mentally impaired and have the same IQ levels as the general population, many will suffer from learning disorders involving arithmetic and spatial skills (map reading, puzzles, visual problem-solving). Children with this problem may also be hyperactive.
If you suspect you have Turner's syndrome, request a karotype study, or a genetic test (via blood test), from your doctor. Fertility drugs will successfully treat Turner's and may alleviate other medical problems associated with it.
There is another disorder you can be tested for, known as Cushing's Syndrome, which is an abnormality of the adrenal gland.
Symptoms include irregular menstrual cycles or no menstrual cycles, a distinctive hump of fat between the shoulder blades, water retention (a.k.a. edema), high blood pressure, obesity, general muscular weakness, and easy bruising. Other characteristics include a moon-shaped face, acne, and abnormal hair growth (similar to PCO).
Some fertility specialists may want to place a woman on what's called a monitored cycle. If blood tests seem to be inconclusive, your doctor may want you to deliver a blood sample each day of your cycle, beginning on day 1. This way, he or she can get a clear picture of which hormones are appearing and disappearing within specific time frames of the cycle. A monitored cycle may also involve ultrasound, which can help establish whether you're developing follicles or whether your uterine is thickening accordingly.
This is an involved process that requires daily trips to a lab or the doctor's office, but the information it yields could nail down a hormonal imbalance. For example, one of the most difficult hormonal problems to diagnose has to do with luteal phase defects, discussed later in this article.
Monitored cycles are also done once you enter treatment, so your doctor knows exactly when you're ovulating for certain procedures such as IVF, IUI, or GIFT.
This is an in-office procedure that involves placing a small plastic cylinder inside the cervix. The cylinder contains a suction device that sucks up only a small portion of the endometrial lining. The lining is then sent to a lab and analyzed. The procedure is an excellent diagnostic tool but is invasive and can be painful. Taking anti-inflammatory medication prior to the procedure will help take the edge off any cramping.
This biopsy procedure is used to investigate hormonal imbalances that can cause irregular cycles or annovulatory cycles, repeated miscarriages, or even irregular uterine bleeding. It takes less than 10 minutes to do and is far less invasive than a laparoscopic procedure.
For an infertility investigation, an endometrial biopsy is usually done
between days 22 and 24 of the menstrual cycle (assuming a 28-day
cycle). At the beginning of that cycle, your doctor will explain the importance of preventing pregnancy for that month. Abstinence or condoms are highly recommended during this interval. Prior to the biopsy, if you have any reason to suspect you're pregnant, a pregnancy test must be done to rule it out.
The purpose of the biopsy is to examine the characteristics of your endometrium to make sure it's the right consistency and thickness for that time of the month, which will indicate whether you're secreting the right combination and levels of hormones. Some doctors may choose to do the biopsy within the first 18 hours of your period, but this is trickier to time and to do. The outcome of your endometrial biopsy will determine whether you have a progesterone deficiency, an estrogen deficiency, or even a luteinizing hormone (LH) deficiency. Depending on the hormonal imbalance, you may just need a hormone supplement.
Prior to taking the test, your doctor will want you to keep a basal body temperature chart during the cycle of test, and perhaps for one cycle following. This will help him or her to put the results into context. You will also have your progesterone levels taken via a blood test on the day of the test.
After the test, you can expect some cramping and spotting. Make sure you don't go home alone in case you have a bad time of it.
Few women will escape an endometrial biopsy during a female workup. This is a very important test that helps to pinpoint hormonal problems that may be suspected through a combination of blood tests, monitored cycles, and charting. While some of you may be recommended for treatment prior to the endometrial biopsy, most doctors will wait for the outcome of this test before recommending treatment.
It usually takes 3-12 months for your cycles to return to normal after going off oral contraceptives (OCs). Roughly 5% of the women who stop using OCs will not see normal cycles for over a year.
In these cases, fertility drugs may be suggested as well. Women who are prone to this usually had irregular cycles prior to taking their OC. It's crucial to note, however, that OCs do not cause infertility; they simply aggravate a preexisting fertility problem. Some of these women may also have hyperprolactinemia.
Fifteen to 25% of irregular ovulation is caused by secreting too much of the hormone prolactin, which interferes with both ovulation and embryo implantation in the uterus.
Prolactin is released from the pituitary gland and is responsible for breast milk production. When levels are high, prolactin stops the pulsing of GnRH from the hypothalamus, which interferes with the pituitary gland's release of FSH and LH, interfering with estrogen and progesterone.
Normally, prolactin levels should be high only if you're pregnant or nursing. Otherwise, high levels can be caused by emotional or physical stress, exercise, nipple stimulation, or large intakes of protein (don't get your prolactin levels tested after you've eaten a giant steak!). Surgery around the rib cage can also raise prolactin levels. Drugs such as amphetamines, tranquilizers, antidepressants, hallucinogens, and alcohol may also be the culprit. If you have either PCO or an underactive thyroid gland (hypothyroidism), you can also have hyperprolactinemia.
Thirty percent of the time, women who have too much prolactin will notice milk in their breasts (called galactorrhea) or will notice milk when they squeeze their nipples during a breast self-exam. Other symptoms might include decreased vaginal secretions and irregular cycles. A woman may also have light, irregular, short, or no periods.
Hyperprolactinemia can be detected by a simple blood test. At least two blood tests will show high levels of prolactin. If the problem is caused by food, you may need to fast before retesting. Often these blood tests are followed up by a CAT scan to check for a possible benign pituitary tumor (occurring in about 5% of all women who have hyperprolactinemia). In fact, with chronically high levels of prolactin, a benign pituitary tumor known as a microadenoma (small) or a macroadenoma (large) is often the cause.
The drug bromocriptine usually offsets prolactin secretion and shrinks any tumors that exist. If a tumor is found, it can be surgically removed through the nasal passage, but this procedure may not restore your fertility. Radiation may also be used to shrink a pituitary tumor, but it's rare in this case.
Premature ovarian failure is when your body goes into premature menopause. Your ovaries just "close shop." This is responsible for about 10% of all ovulation problems and, if you're under 30, your doctor may want to do a chromosome test. This is fairly easy to diagnose through blood tests and a pelvic exam. Some causes include a decreased number of eggs at birth (they get used up earlier), exposure to radiation or chemotherapy, chromosomal abnormalities, diseases such as cancer or AIDS, and physical trauma to the area (injuries and so on). Natural ovarian failure is diagnosed when you have very high levels of FSH and LH in your blood or urine, while your estrogen levels are very low.
In some instances, if your uterus is still healthy, you can have an egg donated and try IVF using your partner's sperm.
This is when you don't have enough progesterone to keep your uterus embryo-friendly. Remember how the follicle bursts, and then turns into a corpus luteum, which secretes progesterone? Well, this stage of your cycle is also called the "luteal phase" and refers to a progesterone deficiency. Most women have a luteal phase that lasts 10-14 days. If your luteal phase lasts for less than 9 days or longer than 14 days, you may have a luteal phase defect. This is diagnosed from a blood test done during your luteal phase (the serum progesterone test) as well as an endometrial biopsy (see below). In this case, two endometrial biopsies are usually done to study variations on the lining's thickness in more detail. A third biopsy may be recommended if there is a question about the results. Your doctor will also look at your BBT chart and monitor your ovaries via ultrasound to try to catch your luteal phase (which will follow your follicular phase).
In a luteal phase defect, the corpus luteum stops working and doesn't produce enough progesterone to keep the endometrium thick enough for an embryo to implant itself. Luteal phase defects may also cause pregnancy loss if the embryo does implant and is a common diagnosis in the event that you have more than two miscarriages. If you conceive with a luteal phase defect, usually the embryo is shed along with the endometrium lining (when you menstruate) before you would discover the pregnancy. This is known as an occult pregnancy.
In general, it's common for women to have luteal phase defects at some point during their menstrual lives. During puberty, around menarche (the first period), during the postpartum phase (after childbirth), and prior to menopause are when luteal phase defects strike the average woman. In these cases, the cycle usually corrects itself. Smoking and stress may also trigger this problem.
The diagnosis of a luteal phase defect has met with some controversy. Many U.K. researchers believe this luteal phase defect is incorrectly labeled; the reason why the corpus luteum is failing is because the follicle it originated from was a dud. In short, if the follicle was a "good egg" to begin with, the corpus luteum would not be failing. According to this line of thinking, if a good egg is produced during the follicular phase of the cycle, then all should go well in the second stage of the cycle. Many U.K. women will be treated with fertility drugs for this problem, in the belief that the drugs will help stimulate the ovaries to produce a better follicle, which in turn will develop into a better corpus luteum.
Most North American doctors, however, feel that treating a luteal phase defect with fertility drugs is akin to putting a bandage on a corpse. The feeling on this continent is that corpus luteum defects have nothing to do with how "good" the original egg is. Instead, the treatment recommended is to compensate for the failing corpus luteum by supplementing this phase of the cycle with progesterone. This will help to prime the endometrium during the luteal phase, making it more receptive to the embryo. These supplements will also help lower a woman's immune system response, preventing it from rejecting the embryo once it does implant. These supplements are given by vaginal or rectal suppository.
When you're taking a progesterone supplement, your doctor will need to monitor you via another endometrial biopsy to make sure that the supplements are working and that the dosage is correct. You'll need to be on these supplements for about 4-5 months before you can expect to conceive. In some cases, the supplements may continue during the first trimester of the pregnancy to reduce the chances of losing the pregnancy due to a lack of progesterone.
If the suppository doesn't work, the "British rules" for treatment are usually
tried next. You'll be put on clomiphene citrate to see if your corpus luteum
improves when your follicle production escalates. But clomiphene citrate, however, may cause luteal phase
problems and even alter cervical mucus in ovulating women. In this case, intrauterine insemination can be
done to compensate for the mucus
problem. Some doctors will supplement either treatment (suppositories or fertility drugs) with an injection of human chorionic gonadotropin (hCG) within the third or fourth day of the luteal phase.
This is usually caused by weight loss, overexercise and stress, anorexia, and bulimia. An underactive hypothalamus or a late puberty may also trigger this problem. The symptoms include very light periods or no periods, and your blood tests will reveal very low hormones and no ovulation. You may have flat temperature readings and no mid-cycle cervical mucus.
If your lifestyle habits are the cause, your doctor will send you home and tell you to gain some weight, stop overexercising, try to relax, and so on. If this doesn't work, you will probably be prescribed a regimen of hormonal supplements or fertility drugs. Even if you're planning on childfree living, women with constant low estrogen levels are at a high risk of developing osteoporosis.
This means "we don't know why you're not ovulating." If you're
ovulating less than 12 times a year and no cause for your irregular cycles are found, you'll be given this "diagnosis." The treatment is to put you on clomiphene citrate and wait. Pregnancy rates in this case are actually quite high.
You'll be relieved to know that ovulatory problems can almost always be treated with fertility drugs. This is known as ovulation induction. Between 60% and 90% of women treated for an ovulatory disorder go on to conceive. There are some drawbacks to fertility drugs, though. Women on clomiphene citrate, for example, may have problems producing high-quality cervical mucus and may not be able to sustain a pregnancy beyond the first trimester due to a luteal phase defect.
As a precaution, don't begin taking ANY fertility drugs before the cause of your ovulatory problems is nailed down. Some doctors tend to prescribe these drugs as soon as they see you're anovulatory, without bothering to find out WHY. In addition, just because you do have a hormonal imbalance doesn't mean there aren't other structural problems at work.
Copyright © 1998 by M. Sara Rosenthal. From The Fertility Sourcebook, by arrangement with The RGA Publishing Group.