Hormone Provider Information

Pharmaceutical Compounding.

Your Solution for Personalization. Your Opportunity for Improved Care.

Pharmaceutical compounding is defined as the practice of preparing customized medications, in accordance with a licensed practitioner’s prescription, to address a patient’s unique set of conditions, tolerances, and preferences where commercially available products are lacking. Pharmaceutical compounding allows providers the flexibility to address unmet needs such as:

Personalize Dosing

Prescribe therapeutically effective dosage strengths that are suitable to the patient without being limited to fixed dosing increments set by commercial products.

Tailor Dosage Forms

Choose a dosage form (capsule, cream, gel, suppository, tablet or other) based on physiochemical compatibility and stability with the active ingredient(s), therapeutic intent, application site, or patient preference.

Eliminate Unwanted Ingredients

Select ingredients that are well tolerated by the patient and avoid ingredients common in commercial therapeutics that a patient may be intolerant, sensitive, or allergic to.

Combine Therapeutics

Consider how active ingredients are best suited together and maximize treatment efficacy, tolerability, and safety. Reduce treatment regimen complexity and enhance patient adherence.

Enhance Compliance

Improve patient adherence by personalizing the medication to produce better therapeutic outcomes, reduce side effects, decrease regimen complexity, or achieve patient preference.

Provide Solutions to Product Unavailability

Create solutions where the commercially available product is not available.

Know How It's Regulated.

CANADA

AUSTRALIA

The State Board of Pharmacy

In the various states, the state's Board of Pharmacy is the primary regulator of pharmacies, including traditional (503A) compounding pharmacies. Each State Board of Pharmacy has written legislations that govern and legally hold compounding pharmacies accountable for all their operations, including compounding itself.

The United States Pharmacopeia (USP)

State Boards of Pharmacy typically adopt in full, in part, or adapted versions of the USP General Chapters that detail standards of practice. For compounding practices, the most noteworthy USP standards of practice are General Chapters USP <795> (Non-Sterile Compounding), USP <797> (Sterile Compounding), and USP <800> (Hazardous Drugs).

The Food and Drug Administration (FDA)

Under Federal law, the FDA has authority over pharmacy compounding and has issued policies on when compounding is appropriate, as well as on the standards for the production of compounded products. Under its authority, the FDA, typically in conjunction with the respective states, inspects compounding pharmacy facilities to ensure compliance with production standards mandated by the USP, and, in the case of outsourcing facilities, with Current Good Manufacturing Practice requirements.

Health Canada

Health Canada oversees the regulation of drugs and health products in Canada, ensuring that the public has access to safe and effective products. Health Canada defines compounding as the combining or mixing of two or more ingredients (of which at least one is a pharmacologically active component) to create a final product in an appropriate dosage form. Health Canada’s Policy of Manufacturing and Compounding Drug Products in Canada (POL-0051) provides information on compounding and establishes a framework to assist in distinguishing between compounding and manufacturing activities of drug products. Under Health Canada’s policy, healthcare professionals engaged in drug compounding must comply with applicable federal/provincial/territorial regulations and standards.

The National Association of Pharmacy Regulatory Authorities (NAPRA)

NAPRA is an association of provincial, territorial and Canadian Armed Forces pharmacy regulatory bodies. The association provides a platform for members to discuss and take a national approach to the practice of pharmacy and pharmaceutical compounding in Canada. NAPRA’s model standards for pharmacy compounding represent the minimum requirements to be implemented by compounding pharmacists across Canada. These standards of practice include those for non-hazardous sterile preparations, hazardous sterile preparations, and non-sterile preparations. The pharmacy regulatory authority of each province or territory can review these model standards and determine how to best implement them in their jurisdiction.

Provincial/Territorial Pharmacy Regulatory Authorities

The pharmacy regulatory authority of each province or territory is the primary regulator of licensed pharmacists and pharmacies, including those who specialize in compounding. The pharmacy regulatory authorities are responsible for administering provincial pharmacy legislation, including legislation on compounding which may be adapted from NAPRA’s model standards for pharmacy compounding. The required adoption of compounding practice standards in each province or territory ensures nation-wide compounding pharmacy accountability, compounding personnel safety, and patient safety.

Therapeutic Goods Administration (TGA)

Compounded medicines are not required to be entered on the Australian Register of Therapeutic Goods if they are extemporaneously prepared for a specific person for a therapeutic use. Additionally, a license to manufacture is not required if the pharmacist is practising in a pharmacy open to the public or a public hospital. However, despite these exemptions, pharmacists are not exempt from meeting advertising requirements or quality standards of the Therapeutic Goods Act 1989 for compounded medications.

Pharmacy Board of Australia (PBA)

The PBA has developed codes, guidelines and policies to provide guidance on the profession of pharmacy in Australia. Detailed guidance to pharmacists who compound medicines is also provided by the PBA to ensure product quality, safety and efficacy. The TGA recommends compounding pharmacists to consider these guidelines in addition to the requirements of the therapeutic goods legislation. The guidelines set forth by the PBA detail the Board’s guidance to registered pharmacists in relation to the compounding (extemporaneous preparation) of medicines, not set out in legislation or a registration standard.

State/Territory Pharmacy Regulatory Authority

Pharmacists must meet their obligations outlined in relevant state or territory (and Commonwealth) legislation as they relate to the preparation, labelling, maintenance of records, storage, dispensing, supply and advertising of compounded medicines. These guidelines outlined from each state or territory also require pharmacists to refer and to meet quality standards set by (but not limited to) the PBA, Australian Pharmaceutical Formulary and Handbook, Therapeutic Goods Act 1989, Pharmaceutical Inspection Convention’s publication, Health Practitioner Regulations Law, or the United States Pharmacopeia for Pharmaceutical Compounding (non-sterile and sterile compounding, Chapters <795> and <797>).

Choose a Pharmacy that Meets and Exceeds Standards

Continuing Education

Has the pharmacy personnel undergone appropriate Continuing Education training and do they have certificates to support this (e.g., hands-on non-sterile lab training, hormone compounding training etc.)?

Quality Assurance & Control

Does the pharmacy have procedures in place for pharmacist verification, batch testing, ingredient testing, and employee testing in accordance with USP standards of practice General Chapter <1163> (Quality Control)?

Standard Operating Procedures

Does the pharmacy have current and compliant Standard Operating Procedures implemented to ensure a robust quality system is in place and compliance with standard of practice (USP <795>, <797>, <800>, <1163>)?

Quality Supply

Does the pharmacy source high quality ingredients that meet pharmacopeia from suppliers with robust vendor qualification and testing programs?

Innovative Technology

Does the pharmacy use innovative technology that ensures greater reproducibility, homogenous mixing, and better quality?

See What It Looks Like.

Efficacy, Safety, & Dosing.

Evidence-Based Medicine Starts Here.

Adrenal hypofunction is a subclinical condition/phenomenon characterized by insufficient secretion of adrenal hormones thought to originate largely from stress (Allen, 2013). Adrenal hypofunction left untreated can impact other hormonal systems resulting in secondary conditions such as estrogen dominance (Wilson, 2001). When compounded therapies are appropriate, compounding opportunities may include topical progesterone, sublingual progesterone, combination therapy, or tailored dosing of DHEA, customized nutraceutical therapy, slow release hydrocortisone among others. Explore efficacy, safety, and dosing evidence below:

Erectile dysfunction is estimated to impact approximately 320 million men worldwide by 2025 (Kapoor & Kapoor, 2016). While current treatments exist, they are often met by barriers such as injection pain, partial efficacy, and dosage forms that don’t suit patient needs (Advanced Urological Care P.C; Mulhall, 2002; Preckshot, 1999). When compounded therapies are appropriate, compounding opportunities for erectile dysfunction may include sublingual options and tailored dosing of common drugs used to manage erectile dysfunction. Explore efficacy, safety, and dosing evidence below:

Estrogen dominance describes increased levels of estrogen relative to those of progesterone, and a number of conditions may be associated with or exacerbated by estrogen dominance such as breast and uterine cancers, fibroids, endometriosis and polycystic ovarian syndrome (US Department of Veterans Affairs). Estrogen dominance is largely managed by restoring the balance with progesterone therapy. Commercially available options of progesterone can be limiting. When compounded therapies are appropriate, compounding opportunities may include tailored dosing of progesterone and alternative dosage forms or routes of administration. Explore efficacy, safety, and dosing evidence below:

Hypothyroidism is one of the most common endocrine disorders, affecting approximately between 6% and 17% of the general population (Biondi & Wartofsky, 2012). Despite the availability of cornerstone therapy, some patients remain undertreated with persistent symptoms prompting the need for personalized regimens, particularly combination forms of therapy (Biondi & Wartofsky, 2012). When compounded therapies are appropriate, compounding opportunities may include combination therapy, customized dosing, tailored ingredient selection to address intolerance, and alternative dosage forms such as slow release capsules. Explore efficacy, safety, and dosing evidence below:

Male hypogonadism has an incidence rate of approximately 6% in middle-aged men and a higher prevalence in older men (Habous et al., 2018). Few treatments available in the U.S. have prompted a higher demand from patients for more diverse and convenient forms of treatment such as those with other modes of administration, fewer adverse effects, and the ability to maintain male fertility (Carrasquillo et al., 2018). When compounded therapy is appropriate, compounding opportunities for male hypogonadism may include transdermal and sublingual dosage forms, tailored dosing, and customized combination therapy. Explore efficacy, safety, and dosing evidence below:

Menopause management with hormone restoration therapy (HRT) is essential for controlling vasomotor and genitourinary symptoms and preventing long-term health complications (e.g., osteoporosis, CV disease). Evaluating the risks and benefits of HRT for menopause has revealed the importance of the type of hormone used (synthetic vs. bioidentical) and the route of administration (oral vs. transdermal) (Simon, 2014). When compounded therapy is appropriate, compounding opportunities for menopause may include bioidentical hormone therapy, tailored dosing, and alternative routes of delivery and dosage forms that are more suitable, safe, and efficacious for the patient. Explore efficacy, safety, and dosing evidence below:

PMS and PMDD is estimated to affect approximately 25% and 5% of women, respectively (Lanza di Scalea & Pearlstein, 2017). Consideration of current treatments and regimens are based on symptom severity, history with previous treatments, contraception needs, conception plans, and modality preferences, thereby forming a patient-tailored approach to care (Lanza di Scalea & Pearlstein, 2017). When compounded therapy is appropriate, compounding opportunities may include combination therapy, tailored dosing, and alternative routes of administration or dosage forms. Explore efficacy, safety, and dosing evidence below:

Sample Formulas^*.

Evidence-Based Medicine Starts Here.

Compounded Medication	Compounding Base	Clinical Reference(s)	Formula Reference
DHEA 10 mg Oral Capsules	CapsuBlend^®-P	Baulieu et al., 2000	F 003 522

* Presented for information and illustration purposes only.

Optimal Base. Optimal Delivery.

Why the Vehicle Matters.

A compounding base serves as a vehicle that carries and delivers the active ingredient(s) to the target site. Bases used in hormone therapy depend on the route of administration or dosage form: creams or gels for topical and intravaginal use; capsules, tablets, or liquids for oral administration; troches or rapid-dissolve tablets for buccal or sublingual administration; suppositories for intravaginal application. Base selection is a critical process pharmacists perform and should be understood by providers prescribing compounded medications. Notably, selecting a compounding base involves considering the following:

The first thing a pharmacist considers when selecting a base is the physiochemical compatibility of the active ingredient with the base. The chosen base must be able to hold the active ingredient without “breaking”. A gel that liquefies after adding the active ingredient would be an example of incompatibility. Noteworthy properties a pharmacist or technician will look for when selecting a base include:

Base compatibility with lipophilic vs. hydrophilic active ingredients (i.e., the solubility of active ingredient in the base).

Base compatibility with salt forms of the active ingredient.

Base carrying capacity with consideration for the concentration or amount of active ingredient.

Base compatibility with thickening effects of active ingredients.

Sometimes confused with compatibility, stability refers to the extent to which a preparation retains, within its ‘shelf-life’, chemical, physical, microbiological, therapeutic, and toxicological stability (USP Compounding Expert Committee, 2014). Stability is determined through stability-indicating testing (e.g., HPLC with degradation). Many bases on the market have undergone stability-indicating testing for common formulas. Although not required to compound a medication, stability-indicating testing is an advantageous feature when selecting a base as it not only confirms stability, but it permits extended beyond-use dating (the “expiry date” assigned to a compounded preparation), which facilitates patient access. Below are sample study reports of stability-indicating studies:

Medisca. (2021). Stability assessment of compounded preparations – Bracketed Estradiol 0.01-10% in HRT Cream Base. View Study Report>

Medisca. (2021). Stability assessment of compounded preparations – Bracketed Progesterone 1-40% in HRT Cream Base. View Study Report>

Medisca. (2022). Stability assessment of compounded preparations – Bracketed Testosterone 0.02-25% in VersaPro™ Gel Base. View Study Report>

Patient tolerance is of course pertinent when selecting the active ingredients, excipients, and base of a medication or formulation. Avoiding certain ingredients due to allergies or sensitivities is an advantage and reason alone for compounding. Patient preference to the type of vehicle (e.g., creams, gels, lotions) is also a factor, especially depending on where the patient is applying the preparation. A happy patient is a compliant patient.

Many compounding bases on the market today have functional properties, where the base is formulated with certain ingredients to facilitate certain effects that may be beneficial for the prescribed treatment regimen. These properties are invaluable and can add to the therapeutic effectiveness of a final compounded preparation. Select a route of administration for noteworthy properties that may be considered for hormone therapy:

Topical/Transdermal

Permeation ability. Permeation through the skin layers is required for transdermal delivery. Selecting a base with penetration enhancers or permeation data would be something a pharmacist would look for in this instance.

Moisturizing properties. This property may be desired for a patient with dry skin or mucosal membranes.

Drying properties. A quick drying property is typically desired at the patient level. Males typically prefer quick drying gels.

Alcohol based. Alcohol solubilizes the skin which can aid in diffusion of active ingredients.

Viscosity. A base with a lower viscosity may be preferred for hormones, due to the thickening effect hormones can have.

Oral

Solubility/absorption properties. Blended bases for capsules contain excipients that complement different solubility/absorption properties. These include hygroscopic, poorly soluble, and highly soluble actives.

Buccal/Sublingual

Melting property. Certain dosage forms require heating or melting the base during the compounding process. A base with a lower melting temperature may be required by certain active ingredients that are heat labile.

Mucoadhesive. This feature is sought after when considering a base for its application to mucosal areas such as the oral cavity.

Dissolution/disintegration properties. These features are important when considering a base for its affect on the time to onset of action of the active ingredient.

Intravaginal

Mucoadhesive. This feature is sought after when considering a base to prolong the residence time and contact time to mucosal areas, such as the vagina.

Moisturizing properties. This property may be particularly effective for the treatment of vaginal dryness, a symptom of vaginal atrophy as a result of menopause.

Viscosity. A base with a mild to high viscosity may be preferred for this region to minimize leakage and overall messy application.

Drug-release rate. This property is important to consider when selecting a suppository base for an active ingredient. For example, hormones are lipophilic active ingredients with a slow-release rate in an oily suppository base vs a moderate release rate in a water-soluble suppository base.

Effect on pH. It is important that the properties of the base are suitable for the vaginal environment where vaginal pH is not affected.

Industry-Leading Compounding Bases for Hormone Therapy

	VersaPro™ Cream Base	HRT Cream Base	VersaPro™ Lotion Base
Description	White, shiny, medium viscosity, oil in water cream Non-greasy, great vanishing properties	White, shiny, low viscosity, oil in water cream Non-greasy, great vanishing properties	White, low viscosity, oil in water lotion Non-greasy, great vanishing properties
Recommended Use	If permeation or stability data is preferred or if moisturizing effects are desired	If compatibility with certain acids is required	If lower viscosity is preferred, which may be the case when working with APIs that have thickening effects (e.g., hormones)
Cosmetically Elegant	✓	✓	✓
HRIPT Tested	✓	✓	✓
Free or Parabens, Mineral Oil, & Fragrances	✓	✓	✓
Suitable for Vaginal Use	✓	✓	✓
Salt Tolerant	✓	x	✓
Compatible with Acids	Low (may experience challenges with certain acids that can be corrected with pH adjustments and LiquidGel Complex™)	✓	✓
Excellent Permeation	✓	✓	✓
Wide pH Stability	✓	✓	✓
Studies	Permeation study: Progesterone (VersaPro™ Cream as control)> Stability-indicating study: DHEA 0.2%-4%, Estradiol 0.01%-0.2%, Estriol 0.04%-0.8%, Progesterone 1%-20%, Testosterone 0.025%-0.5% (Bracketed)> Stability-indicating study: Estradiol 0.01%-10% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.25%, Estriol 0.025%-0.25%, Testosterone 1%-10% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.5%, Estriol 0.025%-0.5%, Progesterone 1%-20% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.5%, Estriol 0.1%-2%, (Bracketed)> Stability-indicating study: Estriol 0.01%-10%, (Bracketed)> Stability-indicating study: Progesterone 1%-40%, (Bracketed)> Stability-indicating study: Testosterone 0.02%-25%, (Bracketed)>	Stability-indicating study: DHEA 0.2%-4%, Estradiol 0.01%-0.2%, Estriol 0.04%-0.8%, Progesterone 1%-20%, Testosterone 0.025%-0.5% (Bracketed)> Stability-indicating study: Estradiol 0.01%-10% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.25%, Estriol 0.025%-0.25%, Testosterone 1%-10% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.5%, Estriol 0.025%-0.5%, Progesterone 1%-20% (Bracketed)> Stability-indicating study: Estradiol 0.025%-0.5%, Estriol 0.1%-2%, (Bracketed)> Stability-indicating study: Estriol 0.01%-10%, (Bracketed)> Stability-indicating study: Progesterone 1%-40%, (Bracketed)> Stability-indicating study: Testosterone 0.02%-25%, (Bracketed)>

Selecting a Device

Control Delivery. Maintain Integrity.

A drug delivery device enables and can enhance the administration and/or introduction of an active ingredient to the body, with the potential to improve efficacy and safety by controlling the amount, use, and exposure of the drug during the administration process. In topical/transdermal and intravaginal routes of administration for hormone therapy, drug delivery devices, such as dispensers, are particularly important, as they require accurate dosing. When evaluating a delivery device for topical delivery, the below factors should be considered:

Metered Dispenser

Does the device accurately dose the medication (e.g., 0.1 mL, 0.5 mL, 1.0 mL) with good air evacuation and minimal priming?

Product Integrity

Does the device maintain product integrity and compatibility?
Does it protect from UV, oxidation, and bacterial contamination?

Patient Safety

Does the device ensure patient safety by reducing exposure to hazardous drugs and being free of latex, BPA, and PVC, among more?

Consumer Demand

Does the device meet consumer demands – is it cosmetically elegant, easy to use, easy to transport?

How to Write a Compounded Prescription.

When Personalized Prescription is Appropriate.

Medication Type

Compounded medication is the medication type.

Drug Name & Strength

Indicate the chemical name of the active ingredient(s), not the trademarked brand name. All individual drugs must be listed, and avoid common or proprietary names (e.g., Magic Mouthwash). Include desired strength, concentration, or percentage of the active ingredient(s).

Dosage Form

Indicate the desired dosage form (e.g., cream, gel, capsule, troche, etc.).

Base

When applicable, indicate the desired base.

Direction for Use

Indicate the desired treatment regimen.

Quantity

Include the desired dispensing quantity and any desired refills. Ask your pharmacist about beyond-use dates (BUDs).

Patient-Specific Special Considerations

Describe the need for the compounded medication; the patient-specific considerations that require a compounded medication, such as excipient requirements (e.g., dye allergy, sugar-free, etc.).

Continuing Education.

Learn When Compounding is Appropriate.

Learn from renowned leaders in personalized hormone therapy - Dr. Tara Scott, MD and Dr. Ken Speidel, PharmD - at LP3 Network's Hormone Seminar events. Attend together with your compounding pharmacist and save. Improved patient care starts with collaborative efforts between providers and continued education.

Personalized Hormone Restoration Therapy:
The Fundamentals