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Clinicians who care for HIV-positive women have been reporting protracted gynecologic infections, increased rates of cervical disease, and menstrual dysfunction for several years. Women living with HIV/AIDS frequently ask questions about how HIV infection and its treatment affect the hormonal systems that regulate reproductive and sexual functioning. For some time now, AIDS activists have demanded serious inquiry into the female-specific aspects of HIV disease.
In a limited way, research scientists have posed specific theoretical questions regarding the manner in which hormonally mediated events, such as pregnancy, are affected by the immunocompromise seen in HIV disease. Many questions posed have sought information to increase the well-being of a fetus, rather than to enhance the care of a woman. Most questions simply remain unanswered, and many concerns have not yet been addressed as subjects for legitimate scientific investigation.
There appears to be a tremendous gap between what women want providers to address, and what "women's issues" are actually getting attention in clinics and in research. Part of the problem is that these questions raise difficult an emotional issues for may clinicians and researchers. A larger problem is the pervasive exclusion of woman as research subjects.
The types of questions women most frequently ask include:
The interactions among the neurologic, endocrine, and immune systems are complex and fascinating. The menstrual and reproductive functions are, of course, only a portion of the endocrine makeup in women, but this discussion looks at the clinical problems involving female sex hormones (particularly estrogen and progestin) that occur in patients immunocompromised by HIV infection. In addition, the use of exogenous female hormones in clients with HIV infection are addressed, along with the known benefits and risks of such medications.
There is clearly a need for female controlled methods for reducing transmission of STD. Unfortunately, barrier methods, with or without spermicides, may cause local allergic reactions which increase vaginal discomfort and may even cause abrasions or ulcerations. Intrauterine devices (IUDs) increase the risk of pelvic inflammatory disease(PID) to an unacceptable one for women who are immunocompromised. In addition, IUDs often lead to heavy blood loss during menstruation.
HIV-positive women whose partners are also HIV positive often ask why they should use barriers. Clinicians can pint out that barriers offer some protection from the burden of other sexually transmitted infections such as warts and herpes, which their sexual partner may harbor. Barriers may also prevent the back-and-forth transmission of silent human papilloma virus (HPV) infection., which may lead to cervical dysplasia. Providers should acknowledge the lack of specific information about the effect of repeated exposure to HIV through semen r vaginal secretions. However, while reinfection may not, technically, occur, such exposure may demand a local immune response in the reproductive tract.
Evidence is convincing that women have more gynecologic problems as immune function declines. It is the role of the primary care provider to educate HIV-positive women to the need for frequent gynecologic examinations and early reporting of symptoms suggesting a problem in the reproductive tract. The relation between HIV and HPV is important in understanding the relationship between immune compromise and cervical disease, and should be described to the patient. Discussion of safer sex and the need for monitoring, treatment, and prophylaxis for vaginal thrush (candidiasis) is also very important.
Unfortunately, there is a tendency to refer women outside of the infectious diseases clinic for Pap smears and other gynecologic care. Since gynecologic care is part of primary care for women, it makes sense that basic gynecologic screening should be provided in the setting where women get their primary care. This is even more critical in women with HIV infection, in whom gynecologic problems are quite common and can become life threatening. Of course, consults with expert, sensitive gynecologists should be readily available.
While an asymptomatic HIV-positive woman with good immune function (defined as CD4 count above 400) may not be at any greater risk for cervical cancer than other women, immune function in these patients is less stable. Until further information is available, it seems prudent to schedule women for Pap smears every six months, to treat all gynecologic infections aggressively, to schedule women for follow-up visits when infections occur, and to refer them for colposcopic evaluations for all abnormal Pap smears, including recurrent atypias, within six weeks.
HIV-positive women frequently report changes in their menstrual cycles, such as irregular periods, heavier or scantier periods, early onset of menopausal symptoms, or an increase in premenstrual symptoms such as breast pain, cramping, fluid retention, anxiety, and depression.
Current standards of care for HIV-positive women neither approve nor exclude the use of hormone therapy such as hormone replacement for menopause or oral contraceptives for birth control or menstruation regulation. Too often, in an effort to "do no harm", providers withhold hormones from women. Underlying this policy may be the thought that immunosuppressed patients will progress to AIDS within the near future and that, consequently, the potential for long term benefits of such therapy (such as the prevention of osteoporosis by replacement estrogens) is moot. There may also be a subconscious opinion that women with HIV infection become "asexual" or should not have sex and therefore no not have concerns about menstruation, menopause, and sexuality. In fact, HIV-positive women have the same concerns and desires as other women.
Menstrual problems can adversely affect a woman's health during HIV illness. Blood loss from heavy periods can predispose to or exacerbate anemia. Irregular or absent periods may signal significant systemic illness. Decreased estrogen levels may predispose a woman to vaginitis and urethritis.
In women with HIV, symptoms of ovarian failure, such as hot flashes, may be worse at night and may easily be confused with night sweats that may be due, instead, to infections such as tuberculosis or Mycobacterium avium-intracellulare. Atrophic vaginitis and urethritis may be mistakenly and repeatedly treated as vaginal candidiasis on the basis of the woman's complaints, particularly if an appropriate speculum examination and wet mount microscopic examination are not performed. Atrophic vaginitis may be asymptomatic, or it may be very bothersome and eventually lead to openings and sores on the genitals. These symptoms may interfere with normal sleep, appetite, and sexual functioning.
Amenorrhea should be worked up because the differential is extensive. It includes pregnancy, ovarian failure, stress-related hypothalamic failure to stimulate estrogen production, pelvic mass or infection, malnutrition, pituitary tumor, and thyroid disorder. The diagnosis can usually be accomplished in the primary care setting, but, when necessary, a gynecologist should be consulted. Sexually active women should have a pregnancy test. If this is negative and the menses is delayed by two or more months, a pelvic examination should be scheduled to rule out a pelvic mass. If a mass is noted, it should be confirmed by sonogram.
By three months of amenorrhea, basic blood work should include thyroid stimulating hormone (TSH), and a prolactin level to determine if the problem lies outside the reproductive tract. If these values are abnormal, further studies are indicated. If these values are abnormal, further studies are indicated. If these values are normal and pregnancy has been ruled out, the woman can be given a progesterone challenge to induce withdrawl bleeding. If withdrawl bleeding occurs (even a small amount of spotting is a positive test), it is established that the woman is producing estrogen, but she may not be ovulating. Anovulatory woman may be at increased risk of developing endometrial or breast cancer due to constant estrogen unopposed by progesterone. They may be offered cyclic progesterone or oral contraceptives to induce regular shedding of the endometrium. Cyclic progesterone does not offer the protection against pregnancy provided by oral contraception.
If no withdrawal bleeding occurs with the progesterone challenge, the woman is not producing estrogen and has either ovarian failure to produce estrogen or hypothalamic failure to stimulate the production of follicle stimulating hormone (FSH) and leutenizing hormone (LH). This is the appropriate time in the workup to order FSH and LH. Hypothalamic failure will demonstrate low levels of FSH and LH. This type of failure is usually stress related or the result of weight loss and will often resolve without treatment. High levels of FSH prove that the ovaries are being properly stimulated by the hypothalamus and pituitary gland but are not producing estrogen. Ovarian failure can result from premature menopause, autoimmune disease, or a destructive disease of the ovaries. Diagnosis and proper treatment should be established.
Premature menopause appears frequently in HIV illness, and ovarian failure should prompt a consideration of hormone replacement. Theoretically, physiologic doses of replacement estrogen should not cause much concern about drug interaction or alteration of immune response. Hormone replacement is indicated for severe symptoms of menopause such as hot flashes, atrophic vaginitis, urethritis, vaginal dryness and itching, and discomfort during urination. Replacement hormones may also prevent osteoporosis and damage to the cardiac system. The main concern about hormone replacement is that it increases the risk of endometrial and breast cancer. Current regimens combine estrogen with progesterone to reduced this risk. Irregular bleeding must also be worked up. The differential diagnosis includes pelvic infection or neoplasia, cervicitis, sexually transmitted infection, fibroid tumor or ovarian cyst, and anovulatory cycles. Women over age 35 who have intermenstrual or postcoital bleeding should be referred for endometrial biopsy to rule out endometrial cancer.
The use of oral contraceptives in immunocompromised women should not be confused with concerns regarding transmission of HIV or other sexually transmitted infections. The birth control pill has never offered such protection to women or their sexual partners and cannot replace solid advice regarding safer sex and the use of barriers. Women may want birth control pills because they have more control over use of this method; therefore they are more confident of protection from pregnancy. Furthermore, the pill is associated with regular, reasonably scanty menses, which many women view as a benefit and which is also a health advantage to those with other wise heavy menses, who may be anemic or at risk of becoming anemic.
There are many drug interactions to consider when prescribing oral contraceptives, which certainly present a drawback to their use in women who are on numerous AIDS-related therapies. Drugs may enhance or decrease the activity of oral contraceptives, and oral contraceptives may interfere with the metabolism of various medications. Of particular concern are other drugs that are metabolized in the liver, including certain antibiotics, Dilantin, barbiturates, anticoagulants, antihypertensives, bronchodilators, and steroids. It is undocumented whether or not there are significant interactions with nucleoside anitretrovirals. Since it is possible that anergy may be increased in women who take oral contraceptives, PPD and anergy panels should be obtained and read before prescribing oral contraceptives. For women who display anergy and who are currently on the pill, following the institution's policies for tuberculosis screening in anergic patients should be adequate.
Of course the usual precautions for the pill apply to women with HIV as well, including caution regarding use in women with liver disease or elevated liver enzymes. In summary, there seem to be medical and psychological benefits and risks with oral contraceptives in HIV-positive women, and no clear prohibition to their use, it makes sense that the decision be one of informed consent and dialogue between the woman and her primary care provider.
Pregnancy and HIV infection have been covered in many publications. It is the primary care provider's role to initiate a discussion of the client's childbearing goals and to support those goals, while planning helpful interventions to support the client's and her family's health. The occurrence of a pregnancy before such a discussion has taken place represents a crisis in the provider/client relationship, HIV infection alone is rarely the primary factor in a woman's decision whether to initiate or continue a pregnancy.
The immune function, altered during pregnancy, should be carefully monitored by both a primary care provider well versed in HIV infection and an obsetritian/gynecologist. Of special concern is good management of anemia and of genital infections such as herpes simples, genital warts, cervical disease, vaginitis, and urinary tract infection.
DRUG EFFECT
acetaminophen decreased
benzodiazepines increase
theophyllin increase
trycyclic antidepressants increase
Dilantin increase
CLASS EXAMPLES
Seizure Medications Dilantin
phenobarbital
Antibiotics rifampin,
penicillin,
ampicillin,
metronidazole,
trimethoprim-sulfamethoxazole,
tetracycline
Sedtives benzodiazepins
barbiturates
Table 2. Considerations in the Use of Exogenous Female Hormones in Women with HIV Infection
Estrogens Combination Progesterone
estrogen/progestin
Hormonal Contraceptives N/A Consider Drug interactions Irregular bleeding is
(O.C., Depo provera, May increase anergy a frequent side effect.
Norplant, Good efficacy Progesterone may be.
"minipill", etc.) Therapeutic for dysmenorrhea, immunosupressive
hypermenorrhea
Hormone Replacement Unopposed Physiologic levels used N/A
Therapy (HRT) estrogens may in HRT unlikely to cause
increase risk of drug interactions of
endometrial or affect immune response
breast cancer.
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