Endocrine active compounds (EACs) have been linked by some to a wide variety of adverse reproductive/developmental health outcomes in humans. Our scientists and researchers have developed a number of overview documents and fact sheets that examine the most common concerns regarding these possible health effects.

See also section on "Framework for Assessing Weight of Evidence"


Breast cancer
Breast cancer is characterized by atypical cell growth that begins in the tissues of the breast. There are different types of breast cancer. Breast cancer can arise from the cells lining the milk ducts, the milk-secreting glands, skin, fat, connective tissues, and other cells present in the breast. Risk factors for breast cancer include genetic factors (e.g. BRCA1, BRCA2 genes), hormonal factors (early menstruation, late menopause), medications (oral contraceptive pills, hormone replacement therapy, exposure to diethylstilbestrol DES), obsesity, alcohol consumption, and exposure to radiation. However, known risk factors can not account for all documented cases of breast cancer and therefore chemicals that may mimic the actions of estrogen are thought to play a role in the biology of this disease. Hormonal influences are particularly important because they encourage cell growth. High levels of hormones during a woman's reproductive years, especially when they are not interrupted by the hormonal changes of pregnancy, appear to increase the chances that genetically damaged cells will grow and cause cancer.
Fact sheet
Overview Paper

Endometrial cancer
Endometrial cancer, also called uterine adenocarcinoma or uterine cancer, is a cancerous growth of the lining of the uterus or endometrium. Endometrial cancer is the most common type of uterine cancer. Although the exact cause of endometrial cancer is unknown, increased levels of estrogen appear to have a role. One of estrogen's normal functions is to stimulate the build up of the epithelial lining of the uterus. Excess estrogen administered to laboratory animals produces endometrial hyperplasia and cancer. Risk factors associated with endometrial cancer include obesity, hypertension, and polycystic ovarian disease. Increased risk is also associated with nulliparity (never having carried a pregnancy), infertility (inability to become pregnant), early menarche (onset of menstruation) and late menopause (cessation of menstruation). Women who have a history of endometrial polyps or other benign growths of the uterine lining, postmenopausal women who use estrogen-replacement therapy, and those with diabetes also fit into the higher risk category.
Fact sheet

Endometriosis
Endometriosis is a condition in which the tissue that normally lines the uterus (endometrium) grows in other areas of the body, causing pain, irregular bleeding, and frequently infertility. The tissue growth typically occurs in the pelvic area, on the ovaries, bowel, rectum, bladder, and the delicate lining of the pelvis, but it can occur in other areas of the body as well. The cause of endometriosis is unknown. However, a number of theories have been proposed. The retrograde-menstruation theory proposes that endometrial cells (shed during menstruation) may "back up" through the fallopian tubes into the pelvis, where they implant and grow in the pelvic and/or abdominal cavities. The immune-system theory suggests that a deficiency in the immune system allows menstrual tissue to implant and grow in areas other than the uterine lining. Another theory suggests that the cells lining the abdominal cavity may spontaneously develop endometriosis. Risk factors for endometriosis include genetic factors and hormonal factors (early onset of menstrual periods, regular menstrual cycles, and periods lasting 7 or more days).
Fact sheet
Overview Paper

Fecundity and fertility
Fecundity is the potential ability of a couple to conceive a child whereas fertility refers to the ability to conceive and is evaluated by the time to achieve pregnancy. Fertility, or rather, infertility is a growing concern among many couples. It is difficult to determine whether there is an actual increase in age-specific infertility rates as there are few published studies on temporal or geographical trends. Infertility is the inability of a couple to achieve a pregnancy after 12 months of unprotected intercourse. Primary infertility is the term used to describe a couple that has never been able to conceive a pregnancy, after a minimum of 1 year of attempting to do so through unprotected intercourse. Secondary infertility is the term used to describe couples who have previously been pregnant at least once, but have not been able to achieve another pregnancy. Causes of infertility include a wide range of physical as well as emotional factors. Approximately 30% to 40% of all infertility is due to a "male" factor. A "female" factor is responsible for 40% to 50% of infertility in couples. The remaining 10% to 30% may be caused by contributing factors in both partners, or no cause can be adequately identified. In addition to age-related factors, increased risk for infertility is associated with having multiple sexual partners (therefore increasing the risk for STDs), a sexually transmitted disease, a past history of PID (pelvic inflammatory disease), a past history of orchitis (inflammation of the testis) or epididymitis (inflammation of the epididymis; men), mumps (men), a varicocele (dilation (enlargement) of the veins along the vas deferens; men), a past medical history that includes diethylstilbestrol (DES) exposure (men or women), eating disorders (women), anovulatory menstrual cycles, endometriosis, abnormalities of the uterus or cervical obstruction or a chronic disease (e.g. diabetes).
Fact sheet
Overview Paper

Increased rates of spontaneous abortion
A spontaneous abortion also known as miscarriage is the loss of a fetus during pregnancy due to natural causes before fetal development has reached 20 weeks. Pregnancy losses after the 20th week are categorized as preterm deliveries. The term "spontaneous abortion" refers to these naturally occurring events, not elective or therapeutic abortion procedures. The cause of most spontaneous abortions is fetal death due to fetal genetic abnormalities, usually unrelated to the mother. Other possible causes for spontaneous abortion include: infection, physical problems the mother may have, hormone (endocrine) factors, immune responses, and serious systemic diseases of the mother (such as diabetes or thyroid problems).
Fact sheet
Overview Paper

Sex ratios
The sex ratio is defined as the number of live male births divided by the total number of births for a given period of time. It is generally assumed that the sex ratio is stable over long periods of time with about 50:50 male:females. The number of human males, relative to females, born in North America and elsewhere in the world, has been suggested to be declining for several decades. The cause of this change is unknown however environmental chemical exposure is suspected to play a role. A satisfactory mechanistic explanation however has yet to be advanced. Medical factors suggested to reduce the male proportion of offspring include increased paternal and maternal age, the use of techniques such as in vitro fertilization and ovulation induction, non-Hodgkin's lymphoma, hepatitis and multiple sclerosis. Men who develop testicular cancer tend to father more female children than are characteristic of men in the general population. Paternal exposure to therapeutic testosterone appears to produce a greater proportion of male offspring. There may be several reasons why sex ratios may be declining. First, an interuterine endocrine event may be responsible for altered sex ratios. It has also been observed that male and female embryos grow at different rates which may be dependent on the actions of estrogens and other hormones.
Fact sheet

Testicular cancer
Testicular cancer is the abnormal, rapid, and invasive growth of malignant (cancerous) cells in the testicles. Although testicular cancer accounts for 1% of all cancers in men, it is the most common form of cancer in men 15 to 40 years old. Testicular cancers may be classified as seminomas (30-40% of testicular tumors) or non?seminomas (60% of all testicular tumors). The exact cause of testicular cancer has not been identified, however, several predisposing factors may place some men at higher risk. These include a past medical history of undescended testicle(s), abnormal testicular development, Klinefelter's syndrome (a sex chromosome disorder that may be characterized by low levels of male hormones, sterility, breast enlargement, and small testes), or previous testicular cancer. Other factors are under investigation as possible causes, such as exposure to certain chemicals and infection with the human immunodeficiency virus (HIV).
Fact sheet

Ovarian cancer
Ovarian cancer is a cancerous tumor of the ovaries. Ovarian cancer is fairly uncommon, yet it is the 5th leading cause of cancer death in women and the leading cause of death from gynecologic malignancies. The cause is unknown. Older women are at highest risk. More than half of the deaths from ovarian cancer occur in women between 55 and 74 years of age and approximately one quarter of ovarian cancer deaths occur in women between 35 and 54 years of age. Ovarian cancer is disproportionately deadly for a number of reasons. First, symptoms are vague and non-specific, so women and their physicians frequently attribute them to more common conditions. By the time the cancer is diagnosed, the tumor has often spread beyond the ovaries. Second, because no cost-effective screening test for ovarian cancer exists, more than 50 percent of women with ovarian cancer are diagnosed in the advanced stages of the disease. Increased number of ovulatory cycles appears to be a risk factor for ovarian cancer. Therefore, greater number of pregnancies and use of birth control pills (prevents ovulation) appears to have a protective effect. Certain genes may also increase risk, including the breast cancer genes BRCA1 and BRCA2. Patients with a personal history of breast cancer, or a family history of breast and/or ovarian cancer, may have an elevated risk.
Fact sheet
Overview Paper

Prostate cancer
Prostate cancer is a malignant (cancerous) tumor growth within the prostate gland. The cause of prostate cancer is unknown, although some studies have shown a relationship between high dietary fat intake and increased testosterone levels. Prostate cancer is the third most common cause of death from cancer in men of all ages and is the most common cause of death from cancer in men over 75 years old. Men at higher risk include black men older than 60, farmers, tire workers, painters, and men exposed to cadmium. Prostate cancers are classified or staged based on their aggressiveness and how different they are from the surrounding prostate tissue. No preventive measures are known. Adopting a vegetarian, low-fat diet may lower risk. Early identification (as opposed to prevention) is now possible by yearly screening of men over 40 or 50 years old through digital rectal examination (DRE) and PSA (prostate specific antigen) blood test.
Fact sheet
Overview paper

Declining semen quality
With the development of techniques to assist reproduction, semen quality has become a measure of male fertility. A 'semen analysis' or 'sperm count' is a measure of several key parameters (volume, count, motility and morphology) that can assess the man's potential for fathering offspring. Seminal volume normally ranges from 1.5-5 ml/ejaculate. Sperm count is considered normal in most laboratories above 20 million sperm/ml semen. Healthy sperm examined under a microscope are in constant motion which is referred to as 'motility'. 50-60% motility of the sperm contained in an ejaculate is considered normal. The final parameter used to assess the quality of semen is morphology. Morphology refers to the physical shape or appearance of each individual sperm. Abnormal sperm may have deformed heads, tails or midsections, all of which may prevent the normal fertilizing ability of the sperm. Standard value for these parameters has been established by the World Health Organization (WHO) although many fertility laboratories and clinics may use their own standards.
Fact sheet


Male reproductive tract abnormalities
Sexual differentiation is a complicated, hormone-dependent process that determines whether a fetus becomes male or remains female (the default state). This process is triggered by a series of events that must occur with precision and coordination to develop the male reproductive system and associated secondary sexual characteristics. As sexual differentiation is exquisitely sensitive to hormones, male reproductive tract abnormalities may be the result of endocrine disruption. Two common male reproductive tract abnormalities are cryptorchidism, undescended testes after the age of one, and hypospadias, a common abnormality of the penis that appears as an abnormal opening on the underside of the penis rather than at the end. Risk factors for cryptorchidism and hypospadias include ethnicity, family history, use of analgesics during pregnancy, birth order and maternal obesity. Cryptorchidism is a risk factor for the later development of testicular cancer.
Fact sheet
Overview Paper


Precocious puberty
Precocious puberty is premature development of body characteristics that normally occur during puberty. Puberty normally occurs between the ages of 13 and 15 years in boys and between 9 and 16 years in girls. Precocious puberty in females is characterized by onset of sexual development before 8 years of age including any of the following: breast development, appearance of axillary or pubic hair, maturation of the external genitalia and/or onset of menses. There is some evidence that onset of development as early as 7 years of age in Caucasian girls and 6 years of age in African American girls may be considered normal. Precocious puberty in males is defined as the onset of sexual development before 9 years of age including any of the following: enlargement of the testes and penis, appearance of axillary or pubic hair and/or appearance of facial hair usually first noted on the upper lip. As puberty is a hormone-dependent process, it has been speculated that precocious puberty may be a consequence of endocrine disruption.
Fact sheet

Thyroid hormones
The thyroid is a bow tie or butterfly shaped gland located in the neck and hormones secreted by this gland control the way that every cell in the body uses energy (metabolism). These hormones are thyroxine (T4) and triiodothyronine (T3). The secretion of T3 and T4 is controlled by the pituitary gland and the hypothalamus, which is part of the brain. Thyroid disorders may result not only from defects in the thyroid gland itself, but also from abnormalities of the pituitary or hypothalamus. Hypothyroidism, or underactivity of the thyroid gland, may cause a variety of symptoms and may affect all body functions. The body's normal rate of functioning slows, causing mental and physical sluggishness. Lack of adequate thyroid hormone from birth until approximately age 2 years is associated with varying degrees of permanent mental or cognitive impairment. For these reasons most countries in the western world routinely perform screening tests within the first week of life to detect congenital hypothyroidism so that prompt treatment can be initiated to prevent cognitive impairment. Hyperthyroidism or thyrotoxicosis occurs when the thyroid releases too many of its hormones over a short (acute) or long (chronic) period of time. Many diseases and conditions can cause this problem including Graves' disease; non-cancerous growths of the thyroid gland or pituitary gland; tumours of the testes or ovaries. Graves' disease accounts for 85% of all cases of hyperthyroidism.
Fact sheet


Immune System
The immune system is comprised of cells and tissues that recognize "antigens". Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Some non-living substances such as toxins, chemicals, drugs, and foreign particles can be antigens. Substances that contain these antigens are recognized and destroyed by the immune system. Generally, the immune system operates in two ways: Humoral Immunity and Cell-Mediated Immunity. Humoral Immunity involves protein compounds called 'antibodies' or 'immunoglobulins (Ig)'. There are five classes of antibodies: IgG, IgM, IgA, IgD and IgE. These antibodies are released by specialized white blood cells (B-lymphocytes) in response to a foreign antigen. Antibodies bind to the antigen thereby targeting it for destruction or removal. B-lymphocytes 'remember' encounters with foreign cells or organisms and are able to manufacture the correct antibodies upon subsequent exposures. Cell-Mediated Immunity involves another group of specialized lymphocytes T-lymphocytes that control the immune response. T lymphocytes release many types of chemicals, some of which will attract additional lymphocytes to the site of the foreign cells, while others are cytotoxic and cause the death of the foreign cell. Both antibodies and T-lymphocytes are produced specifically against a particular antigen. The endocrine system and the immune system are interdependent to some degree. Certain reproductive hormones have been shown to affect the synthesis of immune chemicals such as cytokines and interleukins. Some autoimmune diseases are more prevalent among women rather than men, suggesting that female reproductive hormones may modulate the female immune system.
Fact Sheet