Appendix C
Glossary
active pharmaceutical ingredient (API): Any substance that is represented for use in a drug and that, when used in the manufacturing, processing, or packaging of a drug, becomes an active ingredient or a finished dosage form of the drug. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure and function of the body of humans or other animals. Elements of a drug that are not an API are called inert pharmaceutical ingredients.1,2
adverse event: An adverse event is any undesirable experience associated with the use of a medical product or preparation in a patient.2
andropause: Also termed “late-onset hypogonadism,” “testosterone deficiency syndrome,” and colloquially, “male menopause,” is a decrease in androgens, especially testosterone, in males that is associated with aging. The origin may be hypothalamic or pituitary (central), testicular, or a combination of both.
bioavailability: The fraction of the administered dose of a drug that reaches the bloodstream for systemic circulation.
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1 Definition from the United States Pharmacopeia.
2 Definition adapted from the U.S. Food and Drug Administration.
bioequivalence: The therapeutic and pharmacokinetic uniformity of two drug products delivered at the same molar dose and under the same conditions.
bioidentical: Sometimes referred to as “bio-identical” or “bio identical,” bioidentical describes hormones that are chemically and structurally identical to those produced by the human body, with the implication that an identical structure translates to an identical physiologic response as endogenous hormones. Bioidentical hormones may be synthesized from plant or animal sources, or completely chemically synthesized; they are offered as U.S. Food and Drug Administration (FDA)-approved products, or products that have not undergone FDA approval.
bulk drug substance: Any substance that is intended for incorporation into a finished drug product or preparation and is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body, but the term does not include intermediates used in the synthesis of such substances.2
clinical need: When used in this report, “clinical need” refers to the condition outlined by Congress in Section 503B of the Federal Food, Drug, and Cosmetic Act as amended by the Drug Quality and Security Act of 2013 that prohibits 503B outsourcing facilities from compounding with a bulk drug substance unless the substance appears on a list established by the U.S. Food and Drug Administration (FDA) identifying which bulk drug substances there is a clinical need for (understood to be when there is no FDA-approved product available to treat the indication the drug is being compounded for).
clinical trial: Any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.
clinical utility: A multidimensional construct that reflects evidence about safety, effectiveness, and therapeutic need.3 Patient preference is also a component, and reflects patients’ individual decision making, based on variable acceptance of benefits and risks.
compounded preparation: A nonsterile or sterile drug or nutrient preparation that is formulated in a licensed pharmacy, outsourcing facility, or other
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3 In the context of this report, therapeutic need relates to the treatment of menopausal and male hypogonadism symptoms.
health care–related facility in response to or anticipation of a prescription or a medication order from a licensed prescriber. Federal law permits compounding; however, these drugs are not U.S. Food and Drug Administration approved for safety and effectiveness.
compounder: An individual who makes compounded preparations. Compounders can be pharmacists, physicians, or individuals under the supervision of a pharmacist, and they may practice in a variety of health care facilities, including pharmacies, hospitals, clinics, and outsourcing facilities.
compounding: Drug compounding is often regarded as the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual patient. Compounding includes the combining of two or more drugs. Compounded drugs are not U.S. Food and Drug Administration approved.2
compounding pharmacy: A pharmacy that makes compounded preparations in response to or anticipation of a prescription order for an individual patient.
conventional hormone therapy: In regard to hormone therapy, conventional refers to U.S. Food and Drug Administration–approved (or equivalent regulatory body) products, which may include conjugated estrogens, progestins, or bioidenticals.
difficult to compound: A condition of both Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act that precludes the use in compounding of those drugs appearing on the list of drugs with a demonstrable difficulty to compound.
drug: For the purposes of this report, considered a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease by affecting the structure or any function of the body.
endogenous: A reference to the originating source of a substance being within the human body.
estrogen: Hormones that bind to estrogen receptors in humans, and exert estrogenic activity. Endogenous estrogens include estrone, estradiol, and estriol.
evidence based: Evidence for efficacy or effectiveness should be based on designs that provide significant confidence in the results. The highest level
of confidence is provided by multiple, well-conducted randomized experimental trials, and their combined inferences should be used in most cases. When evaluations with such experimental designs are not available, evidence for efficacy or effectiveness cannot be considered definitive.
evidence-based medicine: To the greatest extent possible, the decisions that shape the health and health care of Americans—by patients, providers, payers, and policy makers alike—will be grounded on a reliable evidence base, will account appropriately for individual variation in patient needs, and will support the generation of new insights on clinical effectiveness.
excipient: A pharmacologically inactive ingredient used in the formulation of a drug that lends various functional properties to the drug formulation (i.e., dosage form, drug release, etc.).
exogenous: A reference to the originating source of a substance being from outside the human body.
FDA-approved drug product: The finished dosage form that contains a drug substance, generally, but not necessarily in association with other active or inactive ingredients, and has received U.S. Food and Drug Administration (FDA) approval for safety and effectiveness. An FDA-approved drug product will appear in FDA’s Orange Book.
formulation: A selection and mixture of active pharmaceutical ingredients and inactive ingredients, which ideally takes stability, form, and strength into consideration.
hazardous drugs: Any drug identified by at least one of the following criteria: (1) carcinogenicity, teratogenicity, or developmental toxicity; (2) reproductive toxicity in humans; (3) organ toxicity at low dose in humans or animals; and (4) genotoxicity or new drugs that mimic existing hazardous drugs in structure or toxicity. Sites that compound hazardous drugs are required to comply with specific facilities and engineering controls.1
hormone: A diverse class of molecules that influence the activity of other cells throughout the human body. They are excreted from various tissues, circulate in the blood throughout the body, and influence different physiological responses by generating cellular signals through their interactions with ion channels or by binding to and activating a class of proteins called receptors.
hormone pellet: An implant that is inserted subcutaneously and delivers hormones to the body over an extended period of time.
hormone replacement therapy: Though often used synonymously with “hormone therapy,” hormone replacement may connote an intent to restore hormone levels to what they were previous to the individual becoming symptomatic. However, based on clinical guidance, the goal of U.S. Food and Drug Administration–approved therapeutic treatment with hormones is to alleviate symptoms and clinical findings.
hormone therapy: A therapeutic treatment that alters the levels of hormones in the body in order to alleviate symptomology.
hot flushes: Also termed “hot flashes,” are recurring, sudden, and exaggerated sensation of warmth, especially on the face, neck, and chest. Skin may also become reddened at the affected site.
inert pharmaceutical ingredients: An inert, or inactive, ingredient is any substance, other than an “active” ingredient, which is intentionally included in a product. The term “inert” does not imply that the chemical is nontoxic.
mechanism of action: Describes the process by which a drug functions to produce a pharmacological effect.
menopause: A natural event marked by the permanent end of menstruation and fertility due to reduced ovarian function and subsequent decreases in ovarian hormones, confirmed after 12 consecutive months without menstruation.
natural: Describes a hormone drug product derived from a naturally occurring steroid that requires no chemical modification for human administration.
night sweats: Recurring episodes of intense perspiration during sleep, irrelevant of ambient temperature.
off-label: A drug is considered off-label, for example, when an approved drug product is prescribed for a condition, or in a dose, other than that for which it received its approval.
outsourcing facility: A facility that is engaged in the compounding of nonsterile or sterile drugs that has elected to register as an outsourcing facility per requirements of Section 503B of the Federal Food, Drug, and Cosmetic Act. An outsourcing facility may or may not obtain prescriptions for identified individual patients.
pharmacokinetics: The science of drug absorption, distribution, metabolism, and excretion.
progesterone: A hormone produced in the human body by the corpus luteum, placenta, and adrenal cortex that exerts its role in preparing the uterus for pregnancy.
progestin: Hormones with progestogenic activity that are synthesized from various hormone-starting materials and bind to progesterone receptors and exert the same effect as endogenous progesterone.
progestogen: Hormones that bind to progesterone receptors in humans and exert progestogenic (endogenous progesterone-like) activity. Progestogens include progesterone and progestins.
semisynthetic: Describes a hormone derived from a naturally ocurring steroid or sterol that requires chemical synthesis for human administration (e.g., hormones derived from soy and Mexican yams).
synthetic: Describes a hormone that is chemically synthesized from nonsteroidal starting material.
vaginal implant: A medicated object, usually a plastic ring, which is inserted into the vagina for slow, long-term absorption of the active drug(s). Unlike vaginal suppositories or tablets, vaginal implants are not completely dissolved in the vagina and must be removed after a specified duration of time.
vaginal suppository: A drug delivery method that relies on the temperature of the body to melt the solid, waxy base in which the active drug is contained, allowing the drug to be absorbed directly into the vaginal walls.
vaginal tablet: Sometimes called a “vaginal insert,” is similar in appearance to an oral pill or tablet, but it is inserted into the vagina for absorption.
vasomotor symptoms: Both hot flushes and night sweats are considered to be vasomotor symptoms.
vulvovaginal atrophy: Also known by the terms “vaginal atrophy,” “atrophic vaginitis,” and “urogenital atrophy,” vulvovaginal atrophy is a thinning, drying, and inflammation of the vaginal tissue due to decreased estrogen presence in these tissues. Vulvovaginal atrophy most commonly occurs in postmenopausal females, and may consist of one or more of the following symptoms: dryness, itching, irritation, soreness, burning, pain during vaginal intercourse, urinary frequency and/or urgency, urge incontinence, burning sensation during urination, and inability to control urine flow.
