GMHC Treatment Issues 1992 Jun 20; 6(7): 2
For some time, women with HIV illness, health care providers,
and activists have been concerned with the effects of HIV
infection and treatment on women's hormones and the effects of
hormones on HIV infection. Sex hormones are important because
they make up the system responsible for regulating reproduction
and sexual function. Questions about this matter are often
asked by women with HIV and include: "Does HIV lead to
menstrual abnormalities such as missed periods, heavier, or
irregular bleeding?"; "Are these problems caused by AZT?";
"Will my menstrual cramps and problems worsen because of HIV?";
"Am I going through early menopause?"; "Why have I lost my sex
drive?"; and "Can I take birth control pills?" Researchers have
scrutinized how pregnancy impacts HIV infection in HIV-positive
women, but thus far they have barely begun to address these
other important concerns.
The immune system's purpose is to keep the body healthy. Its
job is to recognize what belongs to the body and is therefore
part of it, and what is foreign or "other." It must attack and
remove disease-causing substances and organisms without causing
damage to itself. The immune system is a complicated network of
cells and chemicals, and can be thought of as consisting in two
parts: the humoral system (substances called antibodies) and
the cell-mediated system (mainly white blood cells). Both
systems activate white blood cells, called lymphocytes--T-cells
and B-cells and T- cells (including T4s).
T-cells recognize foreign substances (antigens), attach to
their surfaces, and release substances (lymphokines) which
communicate with B-cells. B-cells then produce unique
substances called antibodies. Each type of antibody formed in
this complicated interaction is highly specific and able to
identify and destroy only one antigen. Immune system
dysfunction can come from an under- or overproduction of any
one or a combination of these substances.
The function of the endocrine system is to communicate and
regulate the body's many complicated activities. This system
works by hormones and other substances that are produced in
organs called glands.* Hormones are sent to distant locations
in the body called "target organs" to communicate specific
instructions that regulate important bodily functions. These
include energy production, growth, body temperature, certain
behaviors, and reproductive and sexual functions.
Menstrual and reproductive functions are only a portion of the
entire makeup of the endocrine system. However, this article
will be limited to the portion of the endocrine system
concerned with reproduction. Menstruation occurs by a
communication between the pituitary gland in the brain and the
ovaries. The menstrual cycle directs the ovaries to produce a
ripe egg approximately once a month during a woman's
reproductive years. The process works as follows:
1. The hypothalamus gland stimulates the pituitary gland,
the brain center which acts as the master switch for the
2. The pituitary gland releases two hormones called
follicle stimulating hormone (FSH) and luteinizing hormone
(LH). These signal the ovary to produce its own hormones
(estrogen and progesterone).
3. Estrogen and progesterone, sometimes referred to as the
female hormones, stimulate the release of a ripe egg, the
thickening of the lining of the uterus, and changes in the
breast. If the egg becomes fertilized it will embed itself in
the thick lining, which becomes the placenta. If the egg is not
fertilized, the lining will be shed from the body as a
4. Estrogen and progesterone levels lessen, signaling the
hypothalamus gland to begin the cycle again.
WHERE ENDOCRINE AND IMMUNE FUNCTION MEET
Research has shown that the endocrine system is affected by: 1)
differences in male and female immune responses; 2)
administering hormones and hormone therapy (as in the case of
oral contraception); 3) pregnancy; and 4) immune deficiency and
gynecological disease. Much of this research has been conducted
in test tubes or animals. Also, many of the reports offer
theoretical explanations for their observations. In other
words, even research fails to describe the real life
hormonal/immunological phenomena in women's bodies.
Differences in male and female immune responses are well
documented. It has been determined that female sex hormones,
especially estrogen and progesterone, have a distinct effect on
immune function. Women seem to be more resistant to a
variety of viral, bacterial, and fungal infections than men.
Women also bear the burden of greater susceptibility to
autoimmune disorders. These occur when the immune system
ends up attacking the body. Examples of autoimmune disorders
include lupus, rheumatoid arthritis, idiopathic
thrombocytopenic purpura (ITP), and thyroiditis. Females are
also more likely to reject transplant organs or grafts than
males. Some researchers speculate that a woman's better ability
to fend off illness may be the reason why women live longer
than men. The exact mechanism for this difference between men
and women, however, is not clearly understood. Apparently, both
humoral and cellular immune activities are more aggressive in
women than men. While sex hormones seem to directly affect
the activity of the immune system, HIV-related implications
remain unexamined at this time.
Hormone problems are often faced by women whose treatment may
be complicated by immune suppression. The use of hormone
therapy, like estrogen replacement for menopause or oral
contraception, has neither been approved nor forbidden for
women with AIDS by current standards of care. Too often, in an
effort to "do no harm," hormones are withheld from patients.
This policy may be reinforced by the mistaken idea that
immune-suppressed patients will all progress to AIDS in the
very near future. There may also be a belief that women with
HIV infection are "asexual," or should not have sex, and
therefore do not have the same concerns that others do about
menstruation, menopause, and sexuality. These attitudes,
unfortunately, only deny women the life-enhancing, considerate
health care which is their right.
HIV-positive women frequently complain of changes in their
menstrual cycles, such as irregular periods, heavier or
scantier periods, or an increase in noted premenstrual symptoms
such as breast pain, swelling, anxiety, depression, and cramps.
It is unknown whether these changes are due to HIV itself or to
specific medications, particularly AZT. Some other variables
that need to be considered include use of other medications,
street drugs like cocaine and crack, and weight loss.
Certain noted menstrual irregularities can adversely affect a
woman's health during HIV illness. For instance, an increase in
the amount of period blood (hypermenorrhea) may predispose a
woman to anemia. Anemia may already be a chronic problem,
especially in women with HIV. Skipped periods (amenorrhea)
requires prompt investigation into possible underlying causes
such as pregnancy, ovarian cyst or failure, and early
Amenorrhea should be investigated in all women, regardless of a
woman's intention to become pregnant in the future. An
endocrine specialist should be consulted if easy diagnosis is
not possible. All heterosexually active women should have a
pregnancy test. All women who have not completed menopause and
who miss two periods should receive a pelvic examination, and
tests to determine if the problem lies outside the reproductive
track (i.e., a thyroid or pituitary tumor). Blood tests include
the thyroid stimulating hormone (TSH) and prolactin levels. If
these values are normal and pregnancy can be ruled out, the
woman is often given progesterone challenge (Provera 10 mg
daily for five days) to induce bleeding. If bleeding occurs,
this establishes that she is producing estrogen, but is not
ovulating. These women are at risk for developing endometrial
or breast cancer due to constant estrogen administration.
If menstruation does not start after a progesterone challenge,
it means that the woman is not producing estrogen and has
either an ovarian failure to produce estrogen, or hypothalamic
failure to stimulate production of FSH or LH. This indicates a
need to run a serum FSH and LH level test to distinguish
between the two causes. Hypothalamic failure will demonstrate
low levels of FSH and LH. Such a failure is usually
stress-related, perhaps due to weight loss, and often will
resolve without treatment. High levels of FSH prove that the
ovaries are not producing estrogen. Ovarian failure can be due
to premature menopause, autoimmune disease, or a destructive
disease of the ovaries. The cause should be diagnosed and
Menopause, the natural ending of the menstrual cycle, is a
normal feature of a woman's life cycle and does not generally
require treatment. However, premature menopause seems to be
more common in immune-suppressed women. Hormone replacement is
indicated for severe symptoms of menopause, such as hot
flashes, irritation of the vagina (vaginitis), and irritation
of the tube through which urine exits the body (urethritis),
vaginal dryness, itch, and discomfort during urination.
Replacement hormones may also prevent osteoporosis and damage
the cardiac system. The main concern about hormone replacement
is that it increases the risk of cancer, due to the use of
estrogen alone. Hormone replacement regimens now include
estrogen and progesterone to reduce the risk of cancer.
In women with HIV, symptoms of ovarian failure such as hot
flashes may be worse at night. They may be commonly mistaken
for night sweats which occur due to TB or MAC. Vaginitis and
urethritis may be mistakenly treated as thrush, or may lead to
openings and sores on the genitals. These symptoms may
interfere with normal sleep, appetite, and sexual activities.
Unlike other hormonal states, pregnancy has been studied with
greater emphasis in humans. It has been observed that the high
levels of sex hormones (particularly progesterone) which exist
during pregnancy induce a state of immunesuppression. This is
logically assumed to be required in order that the pregnant
woman not reject the fetus, which, after all, is a "foreign
object" potentially presenting danger to the immune system.
Several authors note that the combination of hormonal, immune,
and vascular (relating to blood vessel) changes during
pregnancy contribute to an increased incidence of herpes and
outbreaks of anal and genital warts (HPV), which occur with
frequency in pregnant women. Influenza infections also occur
more severely in pregnant women. In general, they tend to be
more susceptible to various viral, bacterial, and fungal
infections than non-pregnant women.
The majority of medical articles published on pregnancy report
a decrease in T4 counts during pregnancy, which is most
apparent in the last months of pregnancy. However, most
researchers feel the decrease in cell immunity is best
described as a decrease in the ratio of the number of T4 cells
to T8 cells. In other words, there are more T8 than T4 cells
during pregnancy, a phenomenon which also occurs in people with
HIV. Other factors observed in pregnancy include an increase
in steroids in the body.
Despite the temporary state of immune suppression, it is
generally felt that pregnancy will not adversely affect
asymptomatic HIV-positive pregnant women. Of course, these
women must receive high-quality prenatal and obstetrical care.
Treatment for gynecological problems in HIV-positive women is
in desperate need of immediate research. In particular need of
attention is the role of human papilloma virus (HPV) which is
thought to complicate cervical cancer. Additionally, ample
documentation exists showing that a depressed immune system
makes women susceptible to severe and hard-to-treat vaginal and
The use of oral contraception in HIV-positive women should not
be confused with concerns regarding transmission of HIV or
STDs. The pill has never offered protection from HIV
transmission to women or their sexual partners. Use of the pill
cannot replace safer sex and the use of latex barriers (condoms
and dams). Women may request the pill because they have more
control over reproduction and may feel more confident of
protection from pregnancy, when this is an important concern.
Further, the pill is associated with regular, reasonably short
and light periods, a benefit that many women enjoy.
HIV-positive women who may be anemic may also benefit from
shorter, lighter periods. However, the negative aspects should
be considered as well.
In research regarding the pill's effect on the female immune
system, a study conducted in 1988 concluded that there are no
significant differences in blood levels of immunoglobulins
(which are substances related to antibodies) in women who take
low-dose oral contraceptive as compared to women who do not.9
However, the ability to produce tetanus antibodies after
receiving a tetanus shot, and the ability to respond
appropriately to the PPD test which injects TB protein under
the skin of the arm to test for active infection, may be
impaired in women taking the pill.l� This gives rise to some
concern that the pill may have an immune-suppressing effect and
may also complicate accurate TB testing in these women.
It is unknown whether the pill has adverse interactions with
other commonly used HIV/AIDS drugs, like AZT. However, some
drug interactions have been documented, and must be considered
(e.g. antibiotics, barbiturates, anticonvulsants, valium, oral
anti-diabetics, prednisone, anti-hypertensives, and tylenol).
The usual precautions against the pill apply to women with HIV
as well. For instance, women with liver dysfunction should not
use the pill, since hormones are metabolized in the liver. In
summary, oral contraceptions have medical and psychological
benefits, as well as risks when used in HIV-positive women.
Therefore, it makes sense that the decision should derive from
a dialogue with a well-informed health care provider.
Finally, clinicians and researchers must address the use of
hormones in pre- and post-operative transsexuals. These clients
are often at risk for HIV infection, or may already be aware of
their HIV-positive status. Additionally, many such patients
have already taken hormones from medical and/or non-medical
sources. Often the hormones are needed to support the desired
secondary sexual characteristics such as absent facial hair,
enlarged breasts, and change in voice quality. Clients may have
had surgical castration (surgical removal of sexual organs)
with vaginal reconstruction, and/or breast augmentation with
implants. The estrogen doses that are commonly taken far exceed
the estrogen doses found in oral contraceptives and
It is a questionable practice to refuse to provide a
prescription for hormones or medical advice. Perhaps a
constructive approach is to supply hormone replacement and work
to reach the minimal dose needed to achieve desired effects.
Consideration for the client's overall health and relative
contraindication, as well as potential for drug interactions,
must become part of the discussion.
In HIV disease, as in all areas of women's health and illness,
menstruation must be placed at the top of the research agenda
so that women's questions can be adequately addressed. More
data and understanding of women's bodies are desperately
needed. Neither the immune system nor the endocrine system in
humans has been fully understood or described. Attempting to
understand and synthesize the subtle interaction between these
two networks in women is not easy. A roundtable discussion
among immunologists, endocrinologists,
obstetrician-gynecologists, neurologists, and women with HIV
infection and their advocates would be especially useful.
*It should be noted that lymph nodes are often mistakenly
called glands. Lymph nodes are not glands, but are actually
small bean-shaped organs widely distributed throughout the
1. Erbach GT and Bahr JM. Enhancement of in vivo humoral
immunity by estrogen: permissive effect of a thymic factor.
Endocrinol 128(3):1352-8, 1991.
2. Grossman C. Regulation of the immune system by sex
steroids. Endocrine Review 5(3): 435-455, 1984; and Hazzard
WR. Why do women live longer than men? Biologic differences
that influence longevity. Postgraduate Medicine 85(5):271-8,
3. Ahmed SA et al . Sex hormones, immune responses and
autoimmune diseases. AJP December 1987 (pp.531-551).
4. Racheve C et al. Sex differences information of
anti-T-cell antibodies. Nature 263:415418, 1976.
5. Gurka G and Rocklin RE. Reproductive immunology. JAMA
258(20):2983-7,1987; and Minkoff HL. Immune effects in Current
Problems in Obstetrics and Gynecology and Infertility: AIDS in
Pregnancy. 12(6):214-217, 1989.
6. Castilla IA et al. Decreased levels of circulating CD4
during normal human pregnancy I Repro Immunol 15:103-111,
7. Schafer A et al. The increased frequency of cervical
dysplasia-neoplasia in women infected with HIV is related to
degree of immunosuppression. Am J Obstet Gynecol 164
(2):593-99 1991, and Roche JK and Crum CP. Local immunity and
the uterine cervix: implications for cancer.
8. Forrest BD. Women, HIV and mucosal immunity. Lancet
337:835-836,1991, Mendling W and Kildovsky U. Immunological
findings in patients with chronically recurrent vaginal
candidiasis and new therapeutic approaches. Mycoses
32(8):386-90,1989; and Kalo-Klein A and Witkin S. Regulation
of the immune response to candida albicans by monocytes and
progesterone. Am J OB Gyn 264 (5):1351-1354,1991.
9. Bisset LR and Griffith JFT. Humoral immunity in oral
contraceptive users: Plasma immunoglobin levels and in vitro
immunoglobin production. Contraception 38(5):567-9,1988.
10. Allen MH. Primary care of women infected with HIV.
Obstet Gynecol Clinics of N Amer 17(3):557-69, 1990.
11. Rhoads JL et al. Oral contraceptives and PID. Am J
Obstet Gynecol 144: 630-35,1982.
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