These guidelines were drafted by M. Joseph Fedoruk, MD, Chairman of the American College of Occupational and Environmental Medicine's (ACOEM) Occupational and Clinical Toxicology Committee. The guidelines were reviewed, modified, and adopted by the Committee and approved by the ACOEM Board of Directors on April 18, 1994.
The purpose of the American College of Occupational and Environmental Medicine's (ACOEM) Reproductive Hazard Management Guidelines is to provide occupational medicine physicians, other health professionals, labor, and management with guidelines for managing potential occupational reproductive health hazards. Reproductive health hazards are defined as chemical, physical, or biological agents that can cause either reproductive impairment or adverse developmental effects. The ACOEM guidelines propose that persons responsible for workplace health and safety should assess their workplaces for potential reproductive hazards and implement appropriate responses for managing such hazards.
Reproductive toxicity can be defined as "the occurrence of adverse effects on the reproductive system that may result from exposure to environmental agents." Reproductive toxicity may be expressed as alterations to the reproductive organs and/or the related endocrine system. Developmental toxicity can be defined as "the occurrence of adverse effects on the developing organism that may result from exposure before conception (either parent), development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism."1,2 Developmental toxicity can include fetal death, structural abnormalities or birth defects, and functional deficiencies or altered growth.
The ACOEM Reproductive Guidelines are based upon the following principles:
- 1. Reproductive health represents one of the major aspects of human life.
- 2. The magnitude of occupational and environmental reproductive and developmental health risks in modern society is not well characterized.
- 3. Scientific, epidemiological and toxicological data concerning the reproductive and developmental health risks of many chemicals, physical agents, and biological agents are limited and, in some instances, nonexistent.
- 4. Industrial exposure limits for most chemical agents, which have been promulgated by the Occupational Safety and Health Act (OSHAct), ie, permissible exposure limits (PELs), or the American Conference of Governmental Industrial Hygienists (ACGIH), ie, threshold limit values (TLVs), have been established without consideration of protection from adverse reproductive or developmental health effects. Consequently, compliance with the Occupational Safety and Health Administration (OSHA) or ACGIH exposure limits for many compounds does not assure protection of reproductive health.
- 5. Employees have a fundamental right to work in an environment that is free of significant reproductive health risks.
- 6. Employees have a fundamental right to know about potential reproductive health risks encountered in the workplace.
- 7. Reproductive policies must avoid sex discrimination and must consider potential adverse effects on males, females, and offspring. In some instances, previous reproductive policies have resulted in the exclusion of woman from jobs because of concern over fetal effects.
This report describes guidelines for occupational health professionals to manage reproductive and developmental risks and uncertainties. The guidelines have been established with the recognition that scientific data concerning the reproductive health effects of many occupational exposures is very limited, and consequently, there is considerable uncertainty about what action should be taken to adequately manage many potential workplace reproductive health hazards.
These guidelines describe measures to be used to assess the magnitude of potential reproductive risks in the workplace and options that can be taken to manage the uncertainty associated with these risks. The objective of the guidelines is to facilitate the protection of workers' reproductive health.
Reproductive and Developmental Toxicity
Reproductive and developmental toxic effects have unique characteristics from other patterns of organ-related toxicity that are limited to a single organ system. Appendix A contains an overview of the reproductive process. The target of toxicity can include either parent or the offspring. Characteristics that distinguish reproductive and developmental toxicity from other toxic effects include: (1) adverse effects in the exposed person may only manifest in the other party. For example, an exposure to a reproductive toxicant in a male may produce an effect in the conceptus; (2) infertility may not become evident until children are desired, and may therefore go unnoticed for long periods; and (3) normal reproductive function is only expressed intermittently.
Disturbances of the reproductive process from occupational reproductive hazards can produce a broad range of potential toxic effects. Table 1 identifies some potential reproductive and developmental toxicity end points.
Reproductive toxicants3 can be considered to act as direct or indirect toxicants, based upon their mechanisms of actions. Direct-acting toxicants do not require metabolic activation and can produce toxicity in two ways. Structural similarities between a direct-acting toxicant and an endogenous hormone may produce an adverse reproductive effect. For example, polychlorinated biphenyls (PCBs) and some organochlorine pesticides such as dichlorodiphenyl trichloroethane (DDT) act as estrogen agonists. Direct-acting toxicants can also produce toxicity because they are chemically reactive and affect cellular components of tissues involved in reproduction. For example, alkylating agents such as some antineoplastic drugs can be directly toxic to oocytes. Indirect-acting agents require metabolic activation after exerting toxicity. Indirect toxicants can become chemically reactive after metabolism or can modulate enzyme-controlled reproductive functions that are integral to intact hormonal homeostasis required for reproduction.
Magnitude of Workplace Reproductive Health Problems
There are no reliable estimates concerning the number of workers who are at significant risk of exposure to reproductive toxicants.4 Currently, only a few agents or conditions have been identified as being capable of producing structural abnormalities or birth defects and are classified as teratogens. Table 2 lists the agents that have been identified as known teratogens or possible human teratogens.
A much broader range of agents is recognized as having an effect on or the potential to produce reproductive or developmental toxicity. Several agents, such as 1,2,-dibromochloropropane and lead, have been recognized to effect human spermatogenesis but are not proven teratogens. Lead is also a developmental toxicant and has been associated with neurobehavioral effects. There are several reasons for this lack of reliable present day information, perhaps the most important reason being limited epidemiologic and toxicologic data.
Limited Epidemiological Data
Epidemiological studies involving reproductive hazards are difficult to perform for several reasons:
- 1. Reproductive and developmental toxicity end points are often difficult to measure. For example, spontaneous abortions commonly occur among the general population and some studies suggest that up to approximately 40% of fertilized eggs abort before the first missed menstrual period.5 Consequently, spontaneous abortions can occur without a woman's knowledge, making monitoring of this marker difficult.
- 2. The frequency of some adverse reproductive health effects is rare, and large sample sizes are necessary for a study to have sufficient power. For example, congenital malformations are diagnosed in approximately 3% of all births, and large populations are required for an epidemiologic study to have sufficient power to detect a difference between exposed and nonexposed groups.6 Erroneous associations can be demonstrated between exposures and effect from studies with lower power.
- 3. Reproductive studies can have confounding factors. Maternal age is associated with several birth abnormalities and diminished fertility, but is also likely to be associated with exposure to chemicals in the workplace. Persons with lengthy occupational histories will also be older. Other confounding factors, such as sexually-transmitted infections, sexual activity, and nutritional status may be difficult to control. Other factors that can affect fertility, such as smoking, alcohol and drug use, general health, and socioeconomic status, are more readily controllable.
- 4. There can be uncertainty regarding the significance of the factor being measured. For example, there is scientific debate concerning which aspects of sperm, eg, number, motility, or morphology, are the most sensitive markers of certain reproductive effects.
Limited Toxicology Data
There is limited or no toxicological information for the majority of industrial chemicals used in industry. Animal developmental toxicity data are available for only 3000 of the 90,000 chemicals that are used in commerce in the United States.4 Furthermore, testing for some of these compounds has been limited and not included in assessment of the effects on males, females, and offspring.
There are several reasons for the limited information concerning the reproductive and developmental toxicity potential of the many industrial compounds. Tests for reproductive effects may not have been required in the past for many industrial chemicals. There is also uncertainty concerning the extrapolation of effects observed in animal toxicology studies to humans because of differences in species sensitivity and extrapolation of effects observed at high doses to low doses. Although information may be lacking for many chemicals, mutagenic agents should be considered to be potential reproductive toxicants since they are genotoxic and could produce adverse outcome from direct actions on germ cells.
Procedures for the Assessment of Reproductive and Developmental Health Risks
The assessment of occupational reproductive and developmental risks, like any risk from an occupational hazard, involves several distinct steps, including hazard identification, dose response assessment, exposure assessment, and risk characterization. For reproductive hazards, there is often very limited information concerning the effects of many chemical agents and there can be considerable uncertainties in determining reliable risk estimates.
This process often requires a multidisciplinary team of occupational health professionals from several disciplines, including occupational medical specialists, toxicologists, obstetricians, gynecologists, and exposure assessment specialists, such as industrial hygienists and other health professionals.
Hazard identification, the determination of whether an agent can cause a given effect, is the first step in assessing whether a workplace contains a significant reproductive hazard. This is a qualitative process involving several steps. The chemical, physical, and biological agents to which employees are potentially exposed in the workplace are identified. Available human and animal reproductive toxicity data for these agents are then reviewed to determine if there is any evidence that exposure to the agent could produce a reproductive health risk. Professional judgment is often required in hazard identification because information concerning the reproductive health hazards of many agents is limited and may be nonexistent. In addition, all chemicals can produce a toxic reproductive effect with sufficient exposure, especially if they produce maternal toxicity. Consultation with a reproductive toxicologist or other qualified health professional may be necessary to determine the significance of a reported reproductive health effect.
There are several sources of information concerning reproductive health risks. Reproductive and developmental toxicity information may be found in Material Safety Data Sheets (MSDSs), however, detailed information concerning the reproductive toxicity potential of many agents may not be included in an MSDS. Absence of reproductive information on an MSDS does not exonerate an agent. Other sources of information include text books, peer reviewed medical and toxicology journals, and toxicology data bases, including some that specialize in reproductive hazards (MEDLINE, TERIS, and the Toxicology Information Program). It is important to recognize that reproductive toxicology is a rapidly evolving field and information contained in textbooks may not be current or may not characterize the reproductive health risks of an agent. Table 3 includes a listing of information sources on occupational reproductive hazards.
For agents for which there are recommended exposure limits, such as PELs, TLVs, or the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limits (RELs), the basis for these exposure limits should be evaluated to determine if they were established with a consideration of protection against reproductive and developmental toxicity. Many exposure limits are based upon protection of some other toxicity end point, such as systemic toxicity, neurotoxicity, sensory irritation, or other health effects.
Exposure assessment can be qualitative or quantitative in nature. Qualitative assessment can be used to enumerate exposures associated with the tasks of a particular job and to estimate on a relative scale (eg, none, negligible, low, medium, high) the magnitude of potential exposure for each listed agent and relevant route. This ranking can be based upon the volume of material present or used, the physical form of the material, volatility, frequency of contact, whether or not the material is contained within a closed system, and any engineering controls that might be in place.
Quantitative ambient air monitoring can then be directed toward those tasks that have the greatest potential for exposure. In some situations, analyses of surface samples and dust, soil, and water samples may be indicated to evaluate other potential exposure pathways. The assessment of potential reproductive and developmental risks associated with a particular job can be directed to those agents to which there is a likelihood of significant exposure.
The dose-response evaluation involves the determination of the relationship between an exposure and an effect. Estimation of the human reproductive health effects of many chemical agents is difficult because of the uncertainty in the extrapolation of animal reproductive toxicity data to humans. This process is often performed in conjunction with hazard assessment since many data sources contain both qualitative and quantitative information.
One approach to the dose-response evaluation entails identification of the relevant reproductive and developmental toxicology and epidemiology studies from the literature for the particular exposure agent. Once all technically acceptable studies are selected, no observed effect levels and the lowest observed effect levels can be determined for each class of reproductive or developmental adverse effect. Appropriate safety factors can then be applied to derive an estimated safe level of occupational exposure, based upon reproductive and developmental health considerations.
Risk characterization is the process of determining the potential health risks of an exposure based upon the site-specific exposure potential and the toxicity potential of the agent. The risk characterization process is based on information obtained in the hazard assessment, exposure assessment, and dose-response assessment, together with an estimate of the uncertainty of the risk estimate.
Reproductive Health Hazard Management Options
The ACOEM Reproductive Hazard Management Guidelines define several options that should be considered in the management of reproductive risks and uncertainties. The consideration of which options should be implemented at a specific workplace should be based on an individualized assessment of the potential risks and characteristics of the population at risk. Before implementation of reproductive health hazard management measures, legal review should be considered to ensure compliance with all federal, state, and other regulations pertaining to discrimination and protection of employees' rights and disabilities. These options are listed in Table 4.
Ideally, if a significant workplace reproductive health hazard is identified, the best option for elimination of the agent is through product substitution. However, the elimination of reproductive hazards is not feasible in all instances because of technological constraints, economic in-feasibility, or scientific uncertainty concerning the magnitude of the risk. Substitution should be carefully evaluated to assure that risk is eliminated and reduced rather than increased by procedural changes or by the toxic properties of the proposed substitute.
If a hazard cannot be eliminated, methods to reduce or limit exposure through the use of engineering controls should be implemented. When engineering controls cannot be implemented, personal protective equipment, including respirators, should be used in situations in which engineering controls are not feasible. Administrative workplace controls can also be considered as a method of limiting exposure, eg, alteration of the work schedule or work duties up to and including temporary reassignment.
Exposure-control monitoring can be accomplished by environmental monitoring, which includes the measurement of chemical or other contaminants in the air and other environmental media such as work surfaces, soil, and water. Exposure-control monitoring is often a central component of a risk-management program because exposure potential can be quantified to determine whether there is an excessive exposure and whether exposure control measures are achieving goals in limiting air concentrations or dispersion of the chemical or other substance in the general environment. Personal monitoring of contaminants in the breathing zone (representative) workers is preferred over general environmental air monitoring because it provides far more accurate measures of worker exposure.
Biological monitoring that involves measurement of a chemical or its metabolites in blood, urine, or other media can be considered an extension of exposure-control monitoring. Biological monitoring has the potential for providing objective data concerning whether exposure control methods are effective because it provides a measure of chemical absorption by all routes, including inhalation, dermal exposure, and inadvertent ingestion. Biological monitoring should only be implemented after consideration of the many variables that can affect test results, including pharmacokinetic data, dose-response relationships, and laboratory quality-control procedures. When these are well known and adequately controlled, biological monitoring provides the best estimate of the dose absorbed.
Employees at risk of exposure to significant reproductive hazards must be informed of the potential health risks, to enable them to reach an informed decision concerning acceptance and continuation of employment in such a position. Employees may be planning to procreate and if the job could involve exposure to agents that could adversely affect their reproductive ability or produce developmental toxicity, then the employees involved should be informed of this risk. This is especially important for teratogens or developmental toxins because an employee could potentially experience toxic effects within the first few weeks of pregnancy without realizing that she is pregnant. Risk communication should be targeted to provide accurate and complete information based upon the best available scientific information.
Recommended or Required Notification of Pregnancy
If despite attempts at engineering or administrative controls, the job involves exposure to teratogens or developmental toxins, the employer may request that the employee provide notification of pregnancy. The purpose of employee notification is to provide an opportunity for counseling of the employee during pregnancy when issues concerning potential reproductive risk are most relevant to the employee. The employer may request information from the employee's personal physician concerning her ability to continue performing tasks associated with her job position. This option is not an adequate substitute for aggressive risk communication because notification may not be received until after the pregnancy is recognized and after the most critical period of fetal development. In addition, employees may choose not to identify themselves as being at risk. Employee notification of intended pregnancy, which is seemingly more intrusive, could offer the advantage of earlier intervention.
Employees may be temporarily reassigned from a job position when there is potential exposure to a reproductive or developmental toxin that cannot be adequately controlled through engineering or work-practice controls alone. Temporary reassignment should also be considered when an individual's medical history or risk factors suggest a need.
When personal protective equipment is required to control exposure, temporary reassignment should be considered in three specific circumstances:
- 1. Pregnancy. An employee indicates that she is pregnant.
- 2. Pre-Conception. A male or female employee indicates an intention to have a child.
- 3. Infertility. A couple has sought medical consultation because of infertility and no cause has been discovered.
Medical surveillance should be considered for populations at risk of exposure to a significant hazard. The components of any medical surveillance program should be based upon the type of hazard, the availability of appropriate tests to evaluate the adverse effects of the specific hazard, and the benefits of early detection. Medical surveillance of the reproductive system can be performed by using two types of screening methods. Reproductive history questionnaires can be administered to a population at risk for the purpose of determining whether there are any unusual patterns or clusters of reproductive health problems. Ideally, information from a control nonexposed population should be collected to serve as a comparison group. End points that can be considered include live births, fetal loss, and birth defects. If potential problems are identified that could be related to occupational exposure, a reassessment of exposure potential and reproductive toxicity data may be required for a work site or a specific industrial process. Medical screening to assess the physiological status of the employee's reproductive system may also be indicated for assessment of unusual reproductive health problems if there is an available and appropriate test. Questionnaires also provide a database that could be used to facilitate a retrospective assessment of the effects of a workplace on reproductive function.
Consultation with an epidemiologist or biostatistician may be necessary to interpret the significance of population data from reproductive health questionnaires. If the population being monitored is small, it may be difficult to establish statistically significant findings large enough to enable a conclusion to be drawn. It is essential that reproductive health information be kept confidential. Appendix B contains a sample reproductive health questionnaire that is recommended for use by OSHA workers covered by the cadmium standard (29 CFR 1910.1027).
Although several laboratory tests are available to assess reproductive function, their use is routine medical surveillance has not been established.7 In general, assessment of male fertility is simpler than female fertility since spermatozoa can be readily obtained by semen analysis and ova are difficult to harvest for analysis. However, collection of semen samples can be viewed as obtrusive. Sperm parameters that can be monitored include concentration and morphology, but any conclusions regarding the significance of a finding must consider variables that can affect one or more semen parameters, such as continence time, use of recreational or therapeutic medications, age, smoking, diet, radiation exposures, elevated scrotal temperature, and testicular trauma.8
Breast Feeding Policy
Employers who allow nursing mothers to work in environments in which they are exposed to substances that could be excreted in breast milk, such as selected organic solvents, metals, and pesticides, should assess whether exposure would be sufficient to produce significant concentrations in the breast milk of employees who are breastfeeding.
Human breast milk has been determined to contain a broad range of chemical contaminants.9Table 5 identifies chemicals that have been found in breast milk. In general, there is no evidence that infants are being adversely impacted by the consumption of the many chemicals found in breast milk, although in some instances infants have received significant exposures. Chemicals found in human milk are generally fat soluble and poorly metabolized. Therefore they persist in body fat. In some instances, mothers with occupational exposures to certain chemicals can have concentrations of chemical contaminants that considerably exceed the levels that are permitted by the Food and Drug Administration in cow's milk.10
Employees should be notified of the potential for accumulation of chemical contaminants in breast milk. Assignment of women who are breast-feeding to positions in which there are exposures that would result in an infant receiving a chemical intake in excess of the recommended daily intake for that agent should be closely assessed.
Paraoccupational Disease Management
Employees should examine the possibility of bringing work contaminants that could affect the development of offspring into the home environment.11 Developmental processes are not limited to the embryonic period during which the basic pattern and formation of organs occurs. Development also occurs during the early postnatal period while organs are adjusting to an extrauterine environment and could be undergoing histological and cytological differentiation.12 The manifestation of such effects can potentially include decrements or aberrations of postnatal function rather than structural defects.
A number of approaches may be used to reduce or avoid contamination of the home environment and thereby protect a developing fetus or developing infant and child. These include improved housekeeping in the workplace, employer laundering of work clothes and protective garments, the construction and use of "clean" and "dirty" change rooms, and mandatory use of showers at the end of the workday.
Prepared by M. Joseph Fedoruk, David C. Logan. Melissa A. McDiarmid, Brian G. Forrester, William G. Hughson, Christopher Holland, Hi E. Newby, and James H. Saunders.
1. US Environmental Protection Agency. Proposed guidelines for assessing female reproductive risk. Fed Regist.
2. US Environmental Protection Agency. Guidelines for developmental toxicity risk assessment. Fed Regist.
3. Mattison DR, Plowhchalk DR, Meadows MJ, All-Juburi AZ, Gandy J, Malek A. Reproductive toxicity: male and female reproductive systems as targets for chemical injury. Med Clin North Am.
4. US Congress, Office of Technology Assessment. Reproductive Health Hazards in the Workplace.
OTA-BA-266. Washington, DC: US Government Printing Office; 1985.
5. Wilcox AZ, Wernberg CR, O'Conner JG, et al. Incidence of early loss of pregnancy. N Engl J Med.
6. Edmonds L, Hatch M, Holmes L, et al. Report of panel II guidelines for reproductive studies in exposed human populations. In: Bloom AD, ed. Guidelines for Studies of Human Populations Exposed to Mutagenic and Reproductive Hazards.
White Plains, NY: March of Dimes Birth Defects Foundation; 1981.
7. National Research Council. Biological Marker in Reproductive Toxicology.
Washington, DC: National Academy Press; 1989.
8. Wyrobeck AJ. Application of human sperm parameters for monitoring. Prog Clin Biol Res.
9. Jensen AA. Chemical contaminants in human milk. Residue Rev.
10. Rogan WJ, Bagniewska A, Damstra T. Pollutants in breast milk. N Engl J Med.
11. McDiarmid MA, Weaver V. Fouling one's own nest revisited. Am J Med.
12. Johnson ME, Newman LM, Schmidt RR. Postnatal effects of prenatal insult. Risk Anal.
Appendix A: The Reproductive Process
The Reproductive Hazard Management Guidelines provide a brief overview of the reproductive process to illustrate the broad range of potential toxic end points or clinical manifestations by which a reproductive toxicant could exert an effect. Reproduction is a complex process requiring interactions among multiple physiological systems. In addition, the two individuals or couple who make up the reproductive unit must also be considered as a target in evaluating reproductive and developmental toxicity.
The reproductive process is not limited to reproductive organs that are governed largely by neuroendocrine influence, but also includes other organs that can indirectly affect reproductive ability.
Male Reproductive Physiology
Male reproductive physiology requires the intact functioning of the neuroendocrine system, which involves several organs including the hypothalamus, anterior pituitary gland, and testes. The hypothalamus, a part of the central nervous system, releases gonadotropin-releasing hormone (GNRH), which acts upon the anterior pituitary gland. The anterior pituitary gland, in response to GNRH, secretes follicle-stimulating hormone (FSH) and luteinizing-hormone (LH). FSH and LH act on the testes. FSH plays a central role in initiating and maintaining spermatogenesis, the process that produces intact functioning sperm. Germ cells, the precursors of adult spermatozoa, are located in the testes and continue to be renewed throughout adult male life in response to FSH stimulation.
LH stimulates testicular Leydig's cells to produce testosterone. Testosterone regulates the release of GNRH. The growth, development, and function of male secondary sex glands, including the penis, prostate, and seminal vesicles, are affected by testosterone. In addition, testosterone probably has a role in the stimulation of sperm production.
The neuroendocrine process is complex and the role of other hormones such as prolactin, which is also secreted by the anterior pituitary gland, are currently being investigated.
Female Reproductive Physiology
Female reproductive physiology is dependent on the intact functioning of the neuroendocrine system, which involves the hypothalamus, anterior pituitary gland and ovaries. The hypothalamus releases GNRH, which acts upon the anterior pituitary gland. In response to GNRH, the anterior pituitary gland secretes FSH and LH.
Embryogenesis and Fetal Growth
After fertilization of the ovum, which occurs between 24 and 48 h after ovulation, cell division occurs over several days to produce a blastocyst. The blastocyst implants in the lining of the uterus within 6 to 7 days after ovulation. The extraembryonic membranes and the germ cell layers, including the endoderm, mesoderm, and ectoderm, are formed in the second to third wk. The period of embryonic development, a critical phase of development, occurs during the eighth to ninth weeks of pregnancy. During this phase, the organs are principally formed, including the brain, heart, eyes, and limbs. During the fetal period from the eighth or ninth wk of pregnancy to gestation, fetal growth is characterized by continued biochemical and physiological maturation.
Appendix B: Sample Reproductive Health Questionnaire
The following questions pertain to reproductive history:
Have you or your partner had a problem conceiving a child?
[ ] yes
[ ] no
If yes, specify:
[ ] self [ ] present mate
[ ] previous mate
Have you or your partner consulted a physician for a fertility or other reproductive problem?
[ ] yes
If yes, specify who consulted the physician:
[ ] self [ ]spouse/partner
[ ] self and partner
If yes, specify diagnosis made:
Have you or your partner ever conceived a child resulting in a miscarriage, still birth or deformed offspring?
[ ] yes
[ ] no
If yes, specify:
[ ] miscarriage
[ ] still birth
[ ] deformed offspring
If outcome was a deformed offspring, please specify type:
Was this outcome a result of a pregnancy of:
[ ] yours with present partner
[ ] yours with a previous partner
Did the timing of any abnormal pregnancy outcome coincide with present employment?
[ ] yes
[ ] no
[ ] no List dates of occurrences:
What is the occupation of your spouse or partner?
For Women Only:
Do you have menstrual periods?
[ ] yes
[ ] no
Have you had menstrual irregularities?
[ ] yes
[ ] no
If yes, specify type:
If yes, what was the approximated date this problem began?
Approximate date problem stopped?
For Men Only:
Have you ever been diagnosed by a physician as having prostate gland problem(s)?
[ ] yes
[ ] no
If yes, please describe type of problem(s) and what was done to evaluate and treat the problem(s):