The Top 5 Blog Posts of 2019

Wed, 11 Dec 2019 16:29:00 GMT

By PCCA

And just like that, The PCCA Blog is closing its first full calendar year in the world. Between January and November of 2019, we published 71 blog posts and attracted tens of thousands of readers just like you, many of whom have subscribed as well. Thank you to all of our readers and subscribers for making it a wonderful year. We’re grateful to be able to produce content that professionals in the pharmacy compounding industry find valuable. Below are some of our top-performing posts of the year, reflecting some of the biggest changes that our area of health care is experiencing along with the ever-present need for research-based clinical information.

1. Notable Changes in the New USP <795>
Even though implementation of the new USP General Chapter <795> has been delayed due to appeals, it is still crucial to have a full and nuanced understanding of it. In this post, PCCA Clinical Compounding Pharmacist Matt Martin, PharmD, addresses notable changes to the new USP guidelines and provides some considerations for implementation.

2. An Innovative Option for Hirsutism: Topical Metformin
Clinically, hirsutism “refers to women with excess growth of stiff, pigmented hair (known as ‘terminal hair’) in a male pattern,” explains PCCA Clinical Compounding Pharmacist Sara Hover, RPh, FAARM. But she has exciting news about a potential option for women with hirsutism as well.

3. Oral vs. Topical Estrogen: What the Literature Is Showing about Health Risk
Compounded bioidentical hormone replacement therapy (BHRT) is an important treatment option for women around the world. Colleagues and patients alike come to experts like Pamela Smith, Nat Jones and Sara Hover for guidance. In this two-part post, they cover this all-too-important topic in the BHRT conversation, showing what current literature says about the usage of oral vs. topical estrogen.

4. Upcoming Changes to PCCA Formulas per the New USP <795>, <797> and <800>
The new and revised USP chapters affect many aspects of compounding, including formulas. In this post, PCCA Director of Formulation Development Melissa Merrell Rhoads, PharmD, details the updates we’re planning to make to our formulas based on the new USP guidelines. Pro tip: Look at the types of updates we’re going to make to our formulas as a guide for changes you should consider in your own.

5. Notable Changes in the New USP <797>
The new USP General Chapter <797> implementation is delayed because of appeals just like USP <795>, and that gives compounders more time to become familiar with it. Let Dylan Herr, RA/QA Development Manager at Eagle, help with that. She understands that this version makes significant revisions to the old one, and in this post, she provides you with an overview of those changes and strategies for implementing them.

We’re hard at work planning more content for 2020 that we hope will help you serve patients and grow your business, so keep an eye on The PCCA Blog. If you like what you see, consider subscribing. We’ll send you email notifications when we publish new posts. And if you’re already a subscriber, sit back and relax. We’ll be in touch.

An Innovative Option for Hirsutism: Topical Metformin

Wed, 23 Jan 2019 17:38:54 GMT

An Innovative Option for Hirsutism: Topical Metformin

By Sara Hover

The term “hirsutism” is of Latin origin, meaning excessive growth of stiff hair, or simply hairiness. The common clinical use of the term refers to women with excess growth of stiff, pigmented hair (known as “terminal hair”) in a male pattern. Specific sites for excess hair are lips, chin, and chest. In approximately 90% of hirsute women, the condition either is caused by an underlying polycystic ovarian syndrome or is idiopathic (of unknown cause).¹

Regardless of the source, patients are always looking for options to help with unwanted hair, and even when the commercial product is available, it may not address everyone’s clinical need. Certainly we should look at balancing the hormones or metabolic disorders, but many times a quick solution is needed. Pharmacists and prescribers thinking outside the box and looking at literature through a different lens can create a new and innovative product to help with patients’ problems.

One option may be topical metformin. It is well known that metformin reduces circulating androgens, which can decrease the occurrence of excess hair in women. Combining this with new research demonstrating a local effect when applied topically for hyperpigmentation, it’s possible that applying metformin topically may inhibit and reduce terminal hair growth.²

Similar thinking is used for some commercial products. A review of eflornithine (Vaniqa®) and the studies that were used in the approval process reveals that the studies were done with both oral and topical eflornithine, but that the mechanism of action in topical application is unknown. That is, even though the topical mechanism of action for eflornithine is unknown, it is approved for topical use.³

Metformin

Metformin is indicated as an off-label treatment for polycystic ovarian syndrome because it reduces circulating insulin, which decreases the concentration of free levels of androgens. A few studies have examined the influence of metformin on hirsutism as the primary end point. Kelly and Gordon—in a 14 month, randomized, double-blind, placebo-controlled crossover trial—demonstrated a modest reduction in hirsutism at the end of treatment.⁴ Also, a six month, randomized, controlled trial of 70 patients with polycystic ovarian syndrome who received metformin along with intense pulse light for hair removal, when compared to intense pulse light alone, demonstrated the superiority of the regimen employing metformin.⁵

Other evidence comes from dermatological research. Dermatologists have looked at metformin in a number of skin disorders, such as hormonal acne, hidradenitis suppurativa and acanthosis nigricans. Very recently, systemic usage of metformin for psoriasis and skin malignancies has shown promising results.

Interestingly, though, topical metformin has also been used in hyperpigmentation disorders. One of the proposed mechanisms for reducing pigmentation involves inhibiting the activity of the enzyme protein kinase C beta. Another study demonstrated that inhibition of this enzyme’s activity not only blocked tanning, but reduced basal pigmentation in the epidermis and hair.⁶

Finally, there is promising evidence when looking again at metformin and insulin. Studies of the local effect of metformin on the growth rate of hair at the follicular level have yet to be investigated. However, studies have shown that hair follicles that are exposed to excessive levels of insulin exhibit a higher growth rate. Conversely, hair follicles maintained in the absence of insulin or at typical levels prematurely entered a catagen-like state. The catagen phase is a transitional phase in which the hair follicle shrinks and is cut off from its blood supply. The hair does not grow during this phase, and melanin production stops.⁷

Adjunct Treatment Options

This new research and new perspective on topical metformin may be helpful to compounders and patients in combination with some of the more well-known options. Here are some of the common options for these patients.

Progesterone

Progesterone is considered an anti-androgen because it competes with androgens for the androgen receptor. Some have suggested that it has an effect on 5-alpha reductase (5-αR)—an enzyme whose main function is converting testosterone to dihydrotestosterone (DHT), a highly active form of testosterone—but the literature does not support this concept. However, if progesterone occupies the androgen receptor, then testosterone or DHT are unable to bind and have an effect.⁸

Azelaic Acid

A prominent theory is that the azelaic acid is responsible for the decreased DHT production, and in fact, research has shown that it inhibits the activity of 5-αR. By suppressing this cycle, hair growth will slow or even stop.⁹

Spironolactone

Spironolactone is an androgen blocker and competes with DHT for binding to the androgen receptor. Studies have also shown spironolactone to have an inhibitory effect on 5-αR. Typically spironolactone is used orally, but it is also used topically to illicit a local effect while minimizing systemic side effects. The downside with a topical preparation is the odor, which is unpleasant and may require the addition of a fragrance.¹⁰

Example Formulas

Based on a review of the literature,¹¹ I would recommend application twice daily for formulas such as these.

PCCA Formula #12900, a combination compounded topical cream in Clarifying™

PCCA Formula #12899, a combination compounded topical cream in VersaBase®

PCCA formulas are only available to PCCA member pharmacies. Interested in gaining access to the 9,500+ formulas in our database? Learn more about joining PCCA here.

If PCCA members have questions about compounding for patients with hirsutism, please contact the PCCA Clinical Services Department at 800.331.2498.

Sara Hover, RPh, FAARM, is a Clinical Compounding Pharmacist at PCCA. She has been a compounding pharmacist for over 20 years and owned Creative Compounds in Prosper, Texas, before joining PCCA in 2013. Her areas of expertise are hormone replacement therapy, women’s health, homeopathics, herbal and vitamin supplements, and nutrition.

A version of this article was originally published the May 2018 issue of the Apothagram, PCCA’s members-only magazine.

References

Yildiz, B. O., Bolour, S., Woods, K., Moore, A., & Azziz, R. (2010). Visually scoring hirsutism. Human Reproduction Update, 16(1), 51-64. https://doi.org/10.1093/humupd/dmp024
Bubna, A. K. (2016). Metformin – For the dermatologist. Indian Journal of Pharmacology, 48(1), 4-10. https://doi.org/10.4103/0253-7613.174388
Bristol-Myers Squibb. (2000). Bristol-Myers Squibb Labeling Vaniqa. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21145lbl.pdf
Kelly, C. J., & Gordon, D. (2002). The effect of metformin on hirsutism in polycystic ovary syndrome. European Journal of Endocrinology, 147(2), 217-221. Retrieved from http://www.eje-online.org/content/147/2/217.long
Rezvanian, H., Adibi, N., Siavash, M., Kachuei, A., Shojaee-Moradie, F., & Asilian, A. (2009). Increased insulin sensitivity by metformin enhances intense-pulsed-light-assisted hair removal in patients with polycystic ovary syndrome. Dermatology, 218(3), 231-236. https://doi.org/10.1159/000187718
Park, H. Y., Lee, J., González, S., Middelkamp-Hup, M. A., Kapasi, S., Peterson, S., & Gilchrest, B. A. (2004). Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation. Journal of Investigative Dermatology, 122(1), 159-166. https://doi.org/10.1046/j.0022-202X.2003.22134.x
Philpott, M. P., Sanders, D. A. & Kealey, T. (1994). Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro. Journal of Investigative Dermatology, 102(6), 857-861.
McCoy, N. L. (2001). Female sexuality during aging. In P. R. Hof & C. V. Mobbs (Eds.), Functional Neurobiology of Aging (pp. 769-779). San Diego, CA: Academic Press.
Stamatiadis, D., Bulteau-Portois, M. C., & Mowszowicz, I. (1988). Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. British Journal of Dermatology, 119(5), 627-632.
Sachdeva, S. (2010). Hirsutism: Evaluation and treatment. Indian Journal of Dermatology, 55(1), 3-7. https://doi.org/10.4103/0019-5154.60342
Lehraiki, A., Abbe, P., Cerezo, M., Rouaud, F., Regazzetti, C., Chignon-Sicar, B., … Rocchi, S. (2014). Inhibition of melanogenesis by the antidiabetic metformin. Journal of Investigative Dermatology, 134(10), 2589-2597. https://doi.org/10.1038/jid.2014.202

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.

THE PCCA BLOG

The Top 5 Blog Posts of 2019

An Innovative Option for Hirsutism: Topical Metformin

An Innovative Option for Hirsutism: Topical Metformin

Metformin

Adjunct Treatment Options

Progesterone

Azelaic Acid

Spironolactone

Example Formulas

References