Female Fertility Finding Out Why Your Periods are Abnormal

Treatment for Hyperprolactinemia
The nature of your treatment depends on the cause of the elevated prolactin. Table 12-4, "Treatment for Hyperprolactinemia," explains a number of treatment options. Except for obvious systemic problems such as thyroid inadequacy and kidney failure, I usually prescribe Parlodel to lower prolactin levels. Parlodel will also reduce pituitary tumor size, should one be present. An oral medication taken with meals, Parlodel as few side effects, is relatively inexpensive, and-should you get pregnant-will not adversely affect your baby. Women with hyperprolactinemia respond well to this medication and their fertility usually returns quite quickly.

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Table 12-4

 

Treatment for Hyperprolactinemia

Pituitary tumor

Parlodel (bromocriptine)

Surgery/X-ray therapy

 

Thyroid insufficiency

Thyroid hormone supplement

 

Adrenal androgen excess

Parlodel

Cortisol

Surgery/X-ray therapy

 

Kidney failure

Kidney transplant

Dialysis

 

Empty sella syndrome

Parlodel

 

Medication

Terminate or change medication

 

Idiopathic (unknown)

Parlodel

 

Damaged Pituitary Gland
If your pituitary gland has been damaged by surgery, tumor, radiation therapy, and/or excessive bleeding during childbirth (Sheehan's syndrome), it may not be able to produce LH and FSH hormones in adequate amounts. To restore function to your ovaries, and your fertility, I must replace these hormones. Pergonal/Humegon/Puregon (LH and FSH) and Metrodin (FSH) are common medications used for this purpose. (See chapter 14.)

Cushing's Disease
Though rare, Cushing's disease is characterized by elevated adrenal stimulating hormone (ACTH) secreted from a pituitary tumor. If you have this disease, you will have excess androgens (male hormones) and possibly excess prolactin (found in 20 percent of women with Cushing's disease). To diagnose this condition, I ask my patients to take a low dose steroid pill at bedtime and I check a cortisol level early the next morning. If detected, this condition can often be corrected by surgically removing the pituitary tumor.

Empty Sella Syndrome
Empty sella syndrome occurs when spinal fluid leaks into the bony chamber (fossa) housing your pituitary gland. Empty sella syndrome may happen because of a congenital weakness, surgery, trauma, or a pituitary tumor. When pressure from the spinal fluid compresses the pituitary gland against the bony walls of the fossa, you may lose LH- and FSH-producing cells, and you may lose your fertility. Lowering your prolactin levels with Parlodel (bromocriptine) and supplementing your LH and FSH levels with gonadotropins (FSH+/-LH) should correct your fertility problem.

Many systems in your body can trick your pituitary gland into producing fewer ovarian stimulants. Like production supervisors, your hypothalamus and pituitary gland monitor ovarian performance by sensing levels of estrogen and other chemicals circulating in your blood. In this way the pituitary knows when to speed up or slow down ovarian production. However, when other hormones get out of balance, the feedback messages from your ovaries become distorted and your hypothalamus and pituitary gland respond inappropriately. When this happens, your periods become irregular and you stop ovulating.

Hepatorenal Disease
Hepatorenal diseases affect your body's ability to filter impurities from your blood. Both your liver (hepato-) and your kidneys (-renal) remove toxins and "old" hormones from your system. If estrogen or adrenal androgens (see discussion of adrenal disease below) are allowed to build up in your blood, they tell the pituitary, "Stop stimulating the ovaries. Don't send out any more LH and FSH." The hypothalamus mistakenly thinks that your elevated estrogen supply is coming from ripening follicles. When the pituitary responds to this message by slowing down FSH production, your immature follicles fail to develop and you stop ovulating.

If you have this problem, artificial blood filtration methods such as dialysis may not be adequate to restore your fertility. Pregnancy may not be advisable, however, since it may place an undue strain on your already compromised physical condition. Once your physician arrests the disease and the filtration systems work, your fertility will return.

Adrenal Disease (DHEAS)
Adrenal diseases usually cause two feedback problems: both excess adrenal androgens and, in 30 percent of these cases, excess prolactin (see above) will lower LH and FSH production and cause anovulation. Several different conditions may contribute to DHEAS elevation:

• Psychological or physical stress

   

• Pituitary, ovarian, or adrenal tumors

   

• Congenital adrenal hyperplasia (an inherited disorder)

Fortunately 30 to 40 percent of the women having mild DHEAS elevation will respond to ovulation induction therapy, without my having to treat the basic cause of the DHEAS elevation. If your prolactin hormone is also elevated, Parlodel will reduce both your prolactin and androgen levels

Women with high androgen levels will show signs of virilization, such as growing a mustache (hirsutism). In these cases I must find out what's causing the elevated androgens and treat this condition. Elevated adrenal androgens are associated with Cushing's syndrome, congenital adrenal hyperplasia, or polycystic ovaries.

Cushing's Syndrome
Cushing's syndrome, another rare disorder, can be identified by the presence of "buffalo hump" (characteristic lump of excess fat located between the shoulder blades), water retention (edema), high blood pressure (hypertension), obesity, weakness, bruising, moon face, acne, hirsutism, and menstrual dysfunction. If you have these classic symptoms, I'll run a test to determine if you have an androgen-secreting tumor. If you do not have a tumor, low-dose cortisol medication will get your adrenal androgen production under control and your fertility will return. If the test shows you do have a tumor, surgical removal of the tumor will restore your ability to ovulate.

Congenital Adrenal Hyperplasia
The classic symptoms of congenital adrenal hyperplasia include significant androgen excess, excessive hair growth, and an enlarged clitoris (clitoromegaly). If you have this inherited disorder, you may be shorter than your peers and you may have a family history of this disease.

Because of an enzyme deficiency, you cannot make cortisol. So the chemicals that your body normally uses to synthesize cortisol build up, and your body uses them to make androgens. The excess levels of androgens suppress ovulation.

I can screen for this disorder with a simple blood test for 17-hydroxyprogesterone. The results may lead me to give you an injection of ACTH into your vein and repeating the blood test.

I can treat this disorder by supplementing your cortisol supply. When I replace your missing hormone, you will stop pumping out the chemicals to make cortisol and your androgen levels will return to normal When this happens, you will begin to ovulate. I will continue to supplement your cortisol supply throughout your pregnancy, with no risk to your baby.

Polycystic Ovaries
Polycystic ovaries occur in 4 percent of women. Women having polycystic ovaries are frequently but not necessarily obese, have few if any menstrual periods, and have abnormal hair growth, which increases with the passage of time. Polycystic ovaries are frequently associated with:

• Ovarian or adrenal dysfunction
• Ovarian or adrenal tumors
• Insulin Resistance (Pre-diabetes)
• Adrenal hyperplasia
• Cushing's disease
• Hyperprolactinemia
• Thyroid disorders

Although many different conditions may cause polycystic ovaries, the basic mechanism for excess androgen production appears to be the same. The theca cells in the ovary make androgen. (You may want to refer to the illustrations of the female reproductive tract and hormone system.) Normally the follicular (granulosa) cells convert this androgen to estrogen. When this chemical process fails, androgens build up, the follicle fails to mature fully, and the immature ovum remains trapped in the ovary. As the next menstrual cycle begins, last month's deteriorated, malfunctioning follicle continues to manufacture androgens. This local supply of male hormone now interferes with new follicular growth.

Month after month follicles form, fail to rupture, and continue producing androgens until the ovary becomes cystic and can no longer function. If I could see these ovaries, they would appear enlarged, smooth, and pearly white: a result of long-term LH stimulation without subsequent ovulation.

When I find your LH level higher than your FSH level, I can be almost certain you have polycystic ovaries. If you are thin, laboratory tests will probably indicate that you also have elevated DHEAS and normal estrogen levels. If you are obese, I will probably find that you have elevated estrogens, because your fat cells are converting your excess DHEAS to estrogen. Thirty to 40 percent of the women with polycystic ovaries will also have elevated prolactin, and many will have abnormally high DHEAS and other androgen levels. If androgen levels are extremely high, I will look for an adrenal or ovarian tumor.

I may find a darkening of your skin under your arms, beneath your breasts and on the nape of your neck. This discoloration, called acanthosis nigricans, may indicate a condition called HAIR-AN syndrome. (hyperandrogenism insulin resistance acanthosis nigricans). While the exact reason that elevated insulin levels interfere with ovulation is not yet known many theories exist. And, we do know that women with elevated insulin levels usually are obese and have elevated androgen levels. While exercise, diet and weight loss are the mainstays for treating this disorder, a new drug, Metformin, offers promise.

We no longer recommend the wedge resection (removal of part of the ovary) once performed for polycystic ovaries. Although this procedure often temporarily restores fertility by reducing the amount of androgen production, the surgery permanently reduces your fertility potential by removing egg-filled tissues. In addition, there's a significant risk for adhesion formation, which can also impair fertility.

If you are undergoing laparoscopy I can use lasers or electrosurgical needles to"shoot" cystic follicles and destroy their androgen-producing capabilities. This surgical procedure may correct an ovulation for a short period of time allowing you to conceive without ovulation induction medication. Unfortunately, after three or four months your ovulation abnormality will return if you do not conceive.

Although many women with polycystic ovaries will respond to Serophene other more potent and expensive ovulation induction techniques are often required. You may also require Parlodel and/or cortisol to lower prolactin and androgen levels. If you have polycystic ovaries, you have a good chance for pregnancy, but finding the ovulation induction scheme that works best for you requires careful planning and monitoring. As I monitor your cycles, I may be forced to change medications or dosages or even cancel a cycle. After you have completed a treatment cycle, my nurse practitioner and I will review your treatment and, if you do not conceive a plan will be established for another cycle. I'll discuss more about ovulation induction in chapter 14.

Hypo/hyperthyroidism
Hypo/hyperthyroidism also distorts the hormonal feedback mechanism. Too little thyroid production (hypo-) may cause two fertility problems: increased prolactin levels and persistent estrogen stimulation. (See "Hyperprolactinemia" above.) Hypothyroidism slows down your metabolism and causes "old" estrogens to build up in your blood. This persistent estrogen stimulation tricks your hypothalamus into believing that your ovary is producing enough estrogen, so it tells your pituitary to reduce LH and FSH stimulation. When this happens, your follicles fail to mature and your ovaries do not produce enough estrogen to trigger the LH spike necessary for ovulation. A thyroid hormone supplement will lower your prolactin levels and improve your estrogen metabolism. If your thyroid is underactive, I will check for antibodies that attack your thyroid gland.

When your thyroid gland produces too much thyroid hormone (hyperthyroidism), your increases and prematurely burns up your estrogen supply so you become hypoestrogenic: you don't have enough estrogen. Since the pituitary never senses that your follicle has reached maturity (signaled by elevated estrogen), it does not release the LH spike to trigger ovulation. Oddly enough, taking a thyroid supplement may turn off the o veractive thyroid gland and return thyroid hormone levels to normal, so that normal ovulatory cycles resume. Surgery to remove the overactive thyroid gland is sometimes necessary.

Obesity
Obesity can also lead to insulin resistance and persistent estrogen stimulation. The large number of fat cells in women weighing over two hundred pounds manufacture enough estrogen to interfere with the ovary-pituitary feedback system. The elevated estrogen tells the hypothalamus and pituitary to stop stimulating follicular development. When you reduce your weight through dieting and a moderate exercise program, fertility will resume.

The successful treatment of hormonal feedback problems affecting the hypothalamus and pituitary gland generally results in pregnancy. Sometimes these women may also require ovulation induction techniques, discussed in chapter 14.

Ovarian Abnormalities
Cysts, tumors, infections, and endometriosis can interfere with the delicate hormonal balance of the ovary and depress follicle development. Surgical removal of abnormal tissues (cysts, tumors, and endometriosis) will often restore ovarian function. Although antibiotic therapy will clear up the infections and restore ovulation I frequently become concerned about the condition of the fallopian tubes following an infection. I'll discuss more about resolving tubal problems in chapter 16.

Premature Ovarian Failure
Premature ovarian failure simply means that the ovaries run out of follicles. For unknown reasons some women go through menopause at an early age. There's evidence that a few of these women may have developed an autoimmune reaction to their own ovarian tissue. When this occurs, antibodies form, attack the ovaries, and destroy vital structures. Other reasons include: surgery, trauma, radiation, and chromosomal. Unfortunately, most of the time we do not know why the ovaries fail prematurely. We can confirm this diagnosis by finding elevated FSH levels.

Unfortunately, when you run out of eggs, you cannot make a baby. However, there are new technologies (oocyte donation) that allow you to experience a normal pregnancy and give birth to a baby. I'll talk more about these wondrous possibilities in chapter 21.

For a quick overview of the sources of ovulatory and menstrual problems, you may wish to examine table 12-5 below.

Pregnancy

 

Hypothalamic Malfunction

Emotional stress (endorphins?)

Amenorrhea

athletica (extreme exercise)

Dieting, poor nutrition, weight loss,low body fat

Anorexia

Idiopathic (drugs, toxins, medications?)

Pituitary Gland Malfunction

Hyperprolactinemia

Tumor

Surgery

Trauma

Empty sella syndrome

Sheehan's syndrome

Cushing's disease

Hormonal Feedback Problems Affecting Pituitary Gland

Hepatorenal disease

Adrenal disease

Cushing's syndrome

Congenital adrenal hyperplasia

Polycystic ovary

Hypo/hyperthyroidism

Obesity (excess estrogen)

Ovarian Abnormalities

Ovarian cysts

Endometriosis

Infection

Premature ovarian failure

 

Incidental Fertility Findings

Asherman's syndrome (adhesions in the uterus)

Cervical stenosis (cervix closed from surgery)

Idiopathic (no identifiable cause)

A Note of Concern

If you have amenorrhea or early menopause, I'd like to caution you that you may be at risk for bone decalcification (osteoporosis). Estrogen is vital for the maintenance of good bone structure. The estrogen-deficient athlete (10 to 50 percent of athletic women), for example, will suffer significant bone deterioration within one to three years. Even if pregnancy is not your goal, you may need to supplement your estrogen supply to prevent fractures and irreversible bone damage. Check with your doctor.

For more information on your initial visit to your physician read the
INCIID Routine Fertility Workup or IVF.com Homepage.

Miracle Babies and Other Happy Endings
for Couples with Fertility Problems
Copyright © 1986 Mark Perloe M.D., and Linda Gail Christie.