Unique Reproductive Challenges
A woman's unique ability to become pregnant and give birth is a thing of joy and wonder, and a cause for celebration for women around the world. The underlying mechanisms involved in allowing birth to occur are extremely complex and encompass a myriad of intimately and intricately related elements. At the same time, there are numerous health issues that can affect a woman's ability to get pregnant, have a healthy pregnancy, and deliver a healthy child, including conditions such as abnormal menstrual function, polycystic ovarian syndrome, gynecologic cancers, endometriosis, pelvic inflammatory disease, and more.
In this chapter we look at the conditions and diseases that play a role in a woman's ability to get pregnant and give birth, the medications that are often prescribed to treat these health challenges, and how these medications may affect a woman's reproductive and overall health. (For your convenience, each medication entry in part two has a subheading titled "Of Special Interest to Women," where we note how a specific medication may affect a woman's reproductive health.) We also discuss the impact medications generally can have on a woman's health during pregnancy and after. These are times in a woman's life when her medication decisions affect not only her but her child as well.
Some women call it their period, others call it the curse. Perhaps you're at the stage in your life when you call it history! Whatever you call it, menstruation is central to a woman's reproductive health. Key elements of your reproductive health are hormones, and the hypothalamus and pituitary gland work together to control six of the main hormones necessary to keep your reproductive system functioning: estrogen, follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), progesterone, and testosterone.
This Is Your Period
Briefly, your menstrual cycle and these hormones work like this: Your hypothalamus releases GnRH, which triggers a chemical reaction in your pituitary gland to produce FSH and LH. In response to the release of FSH and LH, your ovaries produce estrogen, progesterone, and testosterone. The synchronization of all these hormones allows a normal menstrual cycle to occur.
Other substances involved with menstruation include prostaglandins, which cause your uterine muscles to contract so you can shed your menstrual blood. Women who have an excessive amount of prostaglandins in their uterus can experience very painful periods, a condition that is known as dysmenorrhea. Dysmenorrhea involves severe pelvic pain and often nausea and vomiting, back and thigh pain, headache, and other symptoms. An excess of prostaglandins is a cause of primary dysmenorrhea, while women who experience these symptoms as a side effect of other reproductive problems, such as endometriosis, pelvic inflammatory disease, uterine fibroids, or use of an IUD, are said to have secondary dysmenorrhea.
Treating Menstruation and Dysmenorrhea
If you still experience menstruation, chances are you also experience some annoying, uncomfortable, even distressing symptoms. While most women report mild to moderate symptoms of cramping, headache, breast tenderness, and bloating, others suffer more serious effects associated with dysmenorrhea. Statistics on how many women experience dysmenorrhea, range from 10% up to 90%, but the important thing is that if you are sufferingwith severe symptoms, the only statistic you care about is you, and you want relief.
For mild menstrual symptoms, a heating pad or a warm bath may be helpful. Some women report relief from natural remedies such as black cohosh or fish oil, and a limited number of scientific studies do back up their benefits. Effective over-the-counter or prescription nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, mefenamic acid, or naproxen can alleviate cramps and muscle aches, and are also helpful if you have dysmenorrhea, as these drugs reduce the concentrations of prostaglandins.
The FDA has approved the NSAIDs diclofenac, ibuprofen, ketoprofen, meclofenamate, mefenamic acid, and naproxen for treatment of dysmenorrhea. Your health-care provider may also prescribe oral contraceptives along with NSAIDs to treat your primary dysmenorrhea symptoms. If your doctor has determined that your severe menstrual symptoms are associated with another reproductive condition, it is necessary to treat that health issue simultaneously with your dysmenorrheal symptoms.
Menstruation Red Flags: See a Doctor If ...
• Your period suddenly stops for more than 90 days (and you cannot attribute it to pregnancy or menopause).
• Your periods become very irregular after you have had regular cycles.
• Your period occurs more frequently than every 21 days or less often than every 45 days.
• You experience bleeding that is heavier than usual or you require one pad or tampon every 1-2 hours.
• You experience severe pain during your period.
• You bleed for more than 7 days.
• You experience fever and feel ill after using tampons.
Between the start of menstruation and menopause, 10% of women can expect to experience endometriosis. If you are among this 10%, then you arelikely no stranger to the pelvic pain that often--but not always--correlates to your menstrual cycle. For some women the pain occurs at other times of the month, and it can be so intense and debilitating that their lives are turned upside down for days.
What Is Endometriosis?
Endometriosis occurs when endometrial tissue, which should grow only inside the uterus, grows outside the uterus. These endometrial deposits, referred to as endometriomas, can be found on the ovaries, the fallopian tubes, the pelvic sidewall, the rectal-vaginal septum, and cesarean scars. Less often they are found on the appendix, bladder, bowel, colon, intestines, and rectum. Sometimes endometriosis causes adhesions that alter a woman's internal anatomy, and in advanced cases the internal organs can fuse together, causing what is known as a "frozen pelvis."
One of the more disturbing consequences of endometriosis for some women is an inability to have children. It is estimated that 30-40% of women with endometriosis suffer from infertility. If you are having difficulty getting pregnant and you have or suspect you have endometriosis, consult a knowledgeable physician as soon as possible to get a diagnosis. Although currently there is no cure for endometriosis, there are treatments that can significantly improve your quality of life.
Treatments for Endometriosis
Medication, hormones, nutritional therapy, alternative therapies, surgery--women have a variety of treatment options when faced with endometriosis. We focus on medications and hormones, but it is important to mention that some women respond to a holistic treatment approach that includes diet and lifestyle elements along with medical options, although these methods are less well studied.
Your choice of treatments will depend on your specific needs and your age, symptoms, and whether you have fertility issues. Many women rely on several treatment options over a long period of time.
Nonsteroidal anti-inflammatory drugs (e.g., celecoxib, ibuprofen, naproxen) are often used to treat endometriosis because they block the production of inflammatory substances called prostaglandins. Because women with endometriosis produce excess amounts of the prostaglandin PGE2, which causes inflammation, pain, and uterine contractions, NSAIDs canprovide relief. However, because NSAIDs stop production of prostaglandins, these drugs must be taken before the prostaglandins are produced. That means you must begin taking the drugs at least 24 hours before you expect the pain to begin. If you wait until your pain starts, then the NSAIDs cannot stop the prostaglandins that have already been released into your system.
If you are taking NSAIDs to treat menstrual pain, it is recommended that you begin taking the medication at least 24 hours before you expect to start bleeding. If your crystal ball is not working and these events are unpredictable, you may want to begin taking NSAIDs about a week before you expect menstruation to begin. To prevent pain-producing prostaglandins from being released, you need to take the NSAIDs regularly as directed by your physician, typically every 6 hours around the clock. This is important because you want to block the release of any prostaglandins into your system. NSAIDs can also reduce the amount of menstrual bleeding. Important side effects and other information about the NSAIDs celecoxib and ibuprofen can be found in part two.
Other medications to relieve pain associated with endometriosis include acetaminophen (Tylenol) and narcotics (e.g., codeine, morphine). Unlike NSAIDs, these medications do not reduce prostaglandin synthesis, but they can help with existing pain.
Because estrogen stimulates the growth of endometrial tissue both inside and outside the uterus, hormone treatment can be prescribed to regulate estrogen production and inhibit the growth of endometrial lesions, and thus provide symptom relief. Your health-care provider may suggest combined oral contraceptive pills (estrogen plus progesterone) or progesterone/progestins alone. Levonorgestrel (Mirena), which has recently been shown to be effective for endometriosis and is used for this purpose in some countries, has not yet been approved in the United States for endometriosis. Because there are many different types of oral contraceptives and other hormone therapies, it is important that you discuss all the options and their benefits and risks with your health-care provider.
Another type of drug called GnRH (gonadotropin-releasing hormone) analogues has been used to treat endometriosis for more than two decades. Medications in this group include leuprolide and goserelin. Both are injected, and they dramatically lower estrogen levels and stop menstruation, which leads to shrinking and sometimes the disappearance of the endometriomas.
Endometriosis and Infertility
Generally, women who have endometriosis have more difficulty getting pregnant, but this does not mean it is impossible. Studies suggest that women who have mild endometriosis take longer to conceive, while those with moderate to severe disease have more difficulty. Some women turn to surgery or assisted reproductive technologies, or both, for help.
Gynecologic cancers are those that affect a woman's reproductive tract and therefore the ability to conceive and give birth. The five main gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar. A sixth type, fallopian tube cancer, is very rare. Four of the five main gynecologic cancers are typically diagnosed in women age 60 or older. Only cervical cancer is likely (47% of cases) to be diagnosed in women younger than 35. According to the Centers for Disease Control and Prevention (CDC), more than 80,000 women were given a diagnosis of a gynecologic cancer in 2007, and more than 27,000 women died from one of these types of cancer.
How can you help prevent gynecologic cancer or detect it early? Each of these gynecologic cancers has its own signs, symptoms, and risk factors, but there are some similarities as well. Perhaps most important is that if these cancers are detected early, treatment can be very effective. That's why it is critical for you to know your body and to seek medical attention if you recognize any warning signs of gynecologic cancers.
For example, the main cause of cervical, vaginal, and most vulvar cancers is human papillomavirus (HPV) infection, a common sexually transmitted virus. The HPV vaccine is available for women up through age 26 who did not get it at the age recommended by the CDC, which is 11-12 years old. You should also get a regular Pap test, which can detect precancerous changes on the cervix that can be treated so cervical cancer can be prevented. The Pap test does not detect any other type of gynecologic cancer.
Treatments for Gynecologic Cancers
Endometrial and cervical cancers, when identified early, are treated with surgery and/or radiation and do not require chemotherapy. More advanced cancers at these sites and other gynecologic cancers are typically treated usingchemotherapy (drugs that stop or slow the growth of cancer cells), in addition to radiation therapy and/or surgery. The drugs chosen for treatment of gynecologic cancers depend on the type of cancer, stage of cancer, and your overall health. The drugs more often chosen as the "first-line" treatment--those health-care providers usually turn to first--include carboplatin (Paraplatin), cisplatin (Platinol), doxorubicin (Adriamycin), and paclitaxel (Taxol). Second-line treatments include 5-fluorouracil (Adrucil), cyclophosphamide (Cytoxan), etoposide (VePesid), and topotecan (Hycamtin).
Chemotherapy drugs are associated with bothersome side effects, and these are provided in the entries in part two.
Pelvic Inflammatory Disease
Every year, more than 750,000 women experience an episode of acute pelvic inflammatory disease (PID), an infection that affects the uterus, fallopian tubes, and other reproductive organs. The disease can damage the fallopian tubes and tissues in and adjacent to the ovaries and uterus, and lead to complications such as the development of abscesses, chronic pelvic pain, ectopic pregnancy, and infertility. In fact, more than 75,000 women may become infertile each year as a result of PID, and many ectopic pregnancies are associated with the disease.
How Do You Get PID?
Pelvic inflammatory disease is caused by bacteria that invade a woman's reproductive organs via the vagina and cervix. Although many different organisms can cause PID, a significant number of cases are associated with two very common sexually transmitted diseases--chlamydia and gonorrhea. Here's a quick look at both of these common causes of PID. (Read more about STDs under "Sexually Transmitted Diseases, Pregnancy, and Your Baby" below.)
According to the CDC, more than 1.2 million cases of chlamydia were reported in the United States in 2008, while the National Health and Nutrition Examination Survey estimated that nearly 3 million people age 14-39 were infected with Chlamydia trachomatis--the bacteria responsible for chlamydia and which can damage a woman's reproductive organs. About 10-15% of women with untreated chlamydia develop PID.
The danger associated with chlamydia is that although the symptoms(vaginal discharge, burning when urinating) may be mild or nonexistent, that does not stop the bacteria from causing serious and irreversible damage, including infertility, which can occur before women even know they have a problem. Women of childbearing age and who are sexually active are most at risk of contracting chlamydia and of developing PID. You increase your chances of getting PID the more sex partners you have, because there is greater potential for exposure to infectious organisms. You can also get reinfected if your sex partners are not treated.
Gonorrhea is caused by the bacteria Neisseria gonorrhoeae. The CDC estimates that more than 700,000 women and men in the United States get a new gonorrheal infection each year. Symptoms of gonorrhea are similar to those of chlamydia and also are typically mild or don't occur in women. Like chlamydia, the consequences of not treating this sexually transmitted disease can be serious.
Symptoms and Complications
As I've noted, it's easy to dismiss symptoms of PID. Along with an unusual vaginal discharge that may have a foul odor and painful urination, lower abdominal pain is common. Other symptoms include fever, painful intercourse, and irregular menstrual bleeding or spotting.
Because symptoms may be overlooked, women risk complications associated with PID, including permanent damage to their reproductive organs. Scarring in your fallopian tubes and other structures in the pelvic area can cause chronic pelvic pain. Even if the fallopian tubes are only partially blocked or damaged, it can result in infertility. A damaged fallopian tube may also trap a fertilized egg in your tube. If the fertilized egg develops into an embryo in the tube rather than the uterus, it is called an ectopic pregnancy, a condition that can rupture the fallopian tube, causing severe pain, internal bleeding, and death.
Treatment of PID
The good news is that PID can be cured using antibiotics. The less than good news is that if any damage has already occurred, the antibiotics cannot reverse it. Therefore, if you experience pelvic pain or other symptoms of PID, seek medical care immediately. The sooner you treat PID, the better able you will be to prevent severe damage to your reproductive organs. Delaying treatment can result in infertility, the possibility of ectopic pregnancy, and chronic pelvic pain.
PID can be a challenge to treat because often more than one organism is responsible for the infection. That's why health-care providers often prescribe at least two antibiotics to address a wide range of possible culprits. The CDS no longer recommends antibiotics in the fluoroquinolone category for treatment of PID and gonococcal infections. Instead your doctor may prescribe cephalexin (Keflex) or cefotetan (Cefotan) (cephalosporin antibiotics) plus doxycycline (Doryx); clindamycin (Cleocin) plus gentamicin (Garamycin); or ampicillin and sulbactam (Unasyn) plus doxycycline (Doryx). You may also take an NSAID to help relieve pain or discomfort.
Occasionally, women with PID need to be hospitalized if they are severely ill with a high fever and vomiting, are pregnant, have an abscess in the fallopian tube or ovary, or are not responding to other treatments and need intravenous antibiotics. Surgery is rarely necessary.
Polycystic Ovarian Syndrome
About 6 million women in the United States have polycystic ovarian syndrome (PCOS), a condition in which a woman's hormones are out of balance because the ovaries make more androgens (male hormones, like testosterone) than normal. An imbalance of hormones can not only throw your periods out of whack, it can also make it very difficult to get pregnant, cause you to gain weight, contribute to skin problems, and eventually lead to serious problems such as heart disease and diabetes if it is not treated. Women with PCOS are also at an increased risk of uterine cancer.
Polycystic ovarian syndrome gets its name from the fact that most (but not all) women with the syndrome have small cysts on their ovaries. These cysts are follicles (eggs encased in a sac) that were never released during ovulation and remained in the ovaries. Women who have PCOS may have regular periods, but they may not ovulate (anovulatory cycles), which renders them unable to get pregnant.
Although these cysts are not harmful per se, they are the result of and contribute to hormone imbalances. Problems with the thyroid gland or other glandular problems can cause or contribute to a hormone imbalance as well.
Causes and Risk Factors
Even though PCOS is the most common hormonal syndrome affecting women of childbearing age in the world, the causes are not certain. It islikely there is more than one cause, and several possibilities are being considered by researchers:
• Dysfunction in the ovaries' production of testosterone and other male hormones
• A defect in the hypothalamus that causes excessive luteinizing hormone signals that stimulate the ovaries
• High levels of insulin, the result of insulin resistance, which increases the impact of luteinizing hormone on the ovaries
• Genetics--there is some evidence that PCOS may run in families
Symptoms of PCOS
PCOS is a syndrome and not disease, because it is a combination of various symptoms that all share an underlying cause. Some women experience many symptoms while others have only a few, and the severity of each symptom among women varies as well.
Basically, if you have PCOS, the production of testosterone and estrogen are out of balance. This may cause:
• Irregular periods or a lack of periods
• Appearance of facial and/or body hair
• Thinning hair on the scalp
• Insulin resistance, which can cause blood sugar levels to rise and eventually result in diabetes
• Abnormal blood lipid levels
• Weight gain and/or an inability to lose weight
• Darkening of the skin, especially at the nape of the neck
• Less common symptoms include white/gray breast discharge, pelvic pain, and/or development of skin tags
Treating Polycystic Ovarian Syndrome
Aside from medication, which we discuss below, dietary and lifestyle changes can help alleviate PCOS symptoms. Most women who have PCOS are also overweight, and weight loss with a healthy diet can not only helpresolve symptoms by getting hormones back into balance, it can also reduce the risk of diabetes and heart problems. It is recommended that you seek a dietician who has experience working with women who have PCOS who can help you develop an effective eating program. Other steps you can take include regular exercise and stopping smoking, both of which can help reduce the risk of heart problems.
Medications used to treat PCOS include birth controls pills, spironolactone, and metformin (a diabetes medication). If you are trying to get pregnant, your health-care provider may recommend fertility medications.
Sexually Transmitted Diseases, Pregnancy, and Your Baby
Some sexually transmitted diseases (STDs) can cause infertility, as we saw with chlamydia, gonorrhea, and PID. However, STDs can also have a serious, even fatal, effect on your baby if you have one of these infections when you are pregnant. The good news is that bacterial STD, such as bacterial vaginosis, chlamydia, gonorrhea, and syphilis, can be treated and cured with antibiotics without affecting the fetus. STDs caused by a virus, however, such as HIV and genital herpes, can be treated to help reduce the risk of transmitting the virus to the fetus, but the disease cannot be cured.
Here's a look at some common STDs, how they can affect you and your fetus during pregnancy, and how they can be treated. As a precaution, women with an STD should ask their doctor about testing their partner for the disease, and whether they should use a condom or refrain from sex, including oral sex, and for how long.
Bacterial vaginosis is caused by an imbalance between the healthy and harmful bacteria in the vagina. Although controversial, it is thought that some women with bacterial vaginosis may develop PID as a result of the infection. Bacterial vaginosis increases susceptibility to other STDs, such as herpes simplex virus, chlamydia, and gonorrhea. If you have bacterial vaginosis while pregnant, you increase your risk for preterm delivery and for giving birth to an underweight infant. Bacterial vaginosis is treatable with antibiotics, most often clindamycin (Cleocin) or metronidazole (Flagyl).
If you are pregnant and have chlamydia, the infection can be easily treated and cured with antibiotics, typically a single dose of azithromycin. Tetracyclines like doxycycline are contraindicated because they may cause staining of the developing child's teeth. If your sex partner has not been treated appropriately, you are still at high risk for re-infection. Left untreated, chlamydial infections may cause premature delivery. Chlamydia also is a significant cause of early infant pneumonia and pinkeye in newborns.
A pregnant woman can transmit the infection as her baby passes through the birth canal. This can cause blindness, joint infection, or a life-threatening blood infection in the baby. If you have gonorrhea and are pregnant, see your health-care provider immediately for treatment with an antibiotic to help minimize the risk of these complications.
About 1,500 newborns are affected by their mother's genital herpes each year in the United States, and this disease can be very serious for infants. The disease can be transmitted during delivery if you have active herpes; that is, if you are "shedding virus" at the time of delivery. You and your physician should discuss the possibility of a cesarean section to avoid exposing your infant to the virus.
If you learn you have genital herpes while you are pregnant, seek immediate medical treatment, which includes an antiviral medication such as acyclovir (Zovirax) or valacyclovir (Valtrex). Treatment during pregnancy can help reduce the risks to your child. About one-third of children infected with herpes at birth develop skin, eye, or mouth sores that can be resolved in nearly all cases with antiviral treatment. The central nervous system is affected in one-third of infants, who may develop symptoms such as seizures, fever, lethargy, and poor feeding behaviors. The remaining third develop disseminated herpes, which affects multiple organs. Genital herpes that affects the central nervous system and organs (e.g., liver, lungs) in infants can be very serious, and even with immediate treatment some die. Others can end up with serious long-term health problems.
Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). You can be HIV positive and not have AIDS. For most women who have HIV, the virus will not pass to the fetus if they are otherwise healthy, because the placenta provides protection. The infection may cross over, however, in women who have advanced HIV, malnutrition, an in-uterine infection (including an STD), or in those who recently acquired HIV.
Babies can become infected with HIV while in the womb, during delivery, or while breast-feeding. If you are pregnant and have HIV and are not being treated, there is a 25% chance your baby will be infected. With treatment, you can reduce that figure to less than 2%, according to the March of Dimes. The main type of treatment for HIV is antiretrovirals, of which there are about 20 in the United States, including amprenavir (Agenerase), efavirenz (Sustiva), and zidovudine (Retrovir).
Syphilis is an STD that is nearly nonexistent in childbearing heterosexual women in the United States, but some cases still exist. Fortunately, it is easy to cure: A single injection of penicillin can eliminate the disease if you have had syphilis for less than a year. If you are allergic to penicillin, your health-care provider can treat you with other antibiotics. Getting treatment is critical, because the bacteria responsible for syphilis can infect the fetus during pregnancy. Depending on how long you have been infected, you may be at high risk of having a stillbirth or giving birth to an infant who dies shortly after birth. An infant may be infected yet have no signs or symptoms of the disease. If the infant is not treated immediately, however, he or she may develop serious problems such as seizures, or die.
Uterine fibroids are noncancerous growths that appear in or on the uterus in up to 75% of women of childbearing age. Most women are not even aware they have fibroids because in most cases these growths are problem-free, cause no symptoms, and require no treatment. Often they are discovered incidentally during a prenatal ultrasound or a pelvic exam.
In a small minority of women, however, uterine fibroids can cause pelvic pain, increased uterine bleeding, and infertility. Although most fibroids are microscopic or small, some can press on the fallopian tubes and block the passage of sperm or eggs, while others may distort the uterine wall and make it difficult for an egg to implant.
When uterine fibroids are problematic, treatment may include gonadotropin-releasing hormone agonists, such as leuprolide (Lupron), or androgens (male hormones), such as danazol, a synthetic drug similar to testosterone. These drugs can stop menstruation and shrink fibroids. NSAIDs can relieve pain, but they do nothing to shrink the fibroids or reduce bleeding.
If medication does not adequately resolve symptoms or if you and your health-care provider decide that removing the fibroids is necessary, especially if infertility is an issue, there are several surgical techniques that can be used, including uterine artery embolization and myomectomy, and an outpatient procedure called a hysteroscopic resection.
Other Reproductive Challenges
In addition to the conditions discussed already, there are a few other reproductive challenges women face. If you are attempting to get pregnant and are having difficulties, or you are experiencing problems with your periods, some of these factors may be involved:
• Overweight. Estrogen is stored in fat cells and tissues, and an excess of body fat can alter a woman's reproductive cycle.
• Underweight. Women whose body weight is 10-15% lower than normal may experience a lack of menstruation (amenorrhea).
• Use of medications. Some medications, including steroids such as cortisone and prednisone, which are used to treat lupus and asthma, can hinder production of follicle-stimulating hormone and luteinizing hormone and have a negative impact on ovulation if taken at high doses. Older blood pressure medications, such as Aldomet and Largactil, can raise prolactin levels and interfere with ovulation. Thyroid medications also can have an impact on ovulation if dosing is too high or too low. Drugs that affect the central nervous system, such as tranquilizers and anticonvulsives (e.g., valproic acid), can affect prolactin levels and impact menstruation.
• Autoimmune disorder. Problems with infertility can be a complication of some autoimmune disorders, such as diabetes, lupus, rheumatoidarthritis, and thyroid disease (an overactive or underactive thyroid gland).
• Tobacco and alcohol. Smoking may increase the risk of infertility, and as few as one drink per day can interfere with conception in some women.
• Environmental factors. Chronic exposure to high emotional or mental stress, radiation, chemicals (at home and/or at work and in everyday products such as plastics), and food additives and contaminants (e.g., bisphenol A [BPA]) may have an impact on fertility.
THE WOMEN'S PILL BOOK. Copyright © 2012 by Lynn Sonberg. All rights reserved. For information, address St. Martin's Press, 175 Fifth Avenue, New York, N.Y. 10010.