Updates in Male Contraceptive Agents

white round capsules

Male contraceptive agents have been highly anticipated as the next step in contraception innovation. To date, several hormonal agents have been developed and tested for safety and efficacy, with three products: Nesterone with Testosterone gel (NES/T), 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MTNDC), and dimethandrolone undecanoate (DMAU). Currently, NES/T is leading in development and contraceptive ability.[1,2]

NES/T has been formulated as a gel containing Nesterone, also known as segesterone acetate (a “pure” progestin presently found in Annovera) in combination with testosterone. This product has passed phase I and phase IIa trials, and is currently in phase IIb trials with a predicted conclusion date for February 2021.[2] NES/T is formulated as a topical gel that can be applied to the shoulders daily with the drug action of sperm count/development suppression to thresholds that should translate to effective contraception with normal hormonal function.[2]

11β-MTNDC is a 28 day daily use oral tablet formulated to act as similarly to 28 day contraceptive regimens for females. The drug acts as a hormonal suppressant to impair spermatogenesis. It is currently in phase I trials, therefore its extent of efficacy and long term effects is still to be determined.[3]

DMAU is formulated as both a 28 day daily use oral tabletand a long acting injection (dosing frequency to be determined). DMAU has a similar action to 11β-MTNDC, and is also still under early investigation in phase I trials.[4]

Despite the difference in administration routes, these drugs have similar effects on male sex hormones. They suppress brain hormones called “gonadotropins,” which results in profound reduction of endogenous testosterone production. The low levels of testosterone thereby result in a reversible reduction in spermatogenesis within the testicles to the point of sperm development impairment, but not enough to cause lasting hormonal changes as of current trialing.[1] The drugs themselvesact as a supplement in place of the person’s own testosterone to maintain male hormonal functions. Current trialing has noted that each product does have the adverse of effect of minor acne at the beginning of treatment.[2,3,4] Participants also noted their concern with a lack of STI prevention.[5] However, with only low risk adverse effects demonstrated thus far in studies, and participants reporting these methods as “easy” treatment regimens to follow, these products appear acceptable for use in the eyes of the American male population.[2,3]

The utility of these products, if approved, is still being questioned. In one US survey participants stated that they would greatly consider the Nestorone topical gel as a first choice method of contraception. 6 However, based on previous contraceptive studies in the US and the United Arab Emirates, the percentages of men using methods of contraception is roughly 59% and 20% respectively.[7,8] According to a 2017 CDC study on contraception use in the U.S., approximately 42.5 million men (59% of the polled 72 million men in the study) engage in contraception practice.[7] With only just over half of the US male population reporting the use of contraception, it is understandable that drug marketing could be seen as risky to pharmaceutical companies if the products are still only in development.

The major obstacles to further drug development are marketing based support and acknowledgment. With only one major organization funding the research on these products, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, progress is very slow.[1] No major pharmaceutical marketing companies have made any public statements on male contraception as a new drug category, it may take longer than the full trialing time to hear more on product availability in the market.

These novel products, NES/T gel, oral DMAU and 11β-MNTDC, if proven to be effective contraceptive agents, would constitute a suitable alternative for couples that wish to participate in planned parenting, but wish to avoid or cannot use contraceptives indicated for females. Although the rate of progress is slow, it is substantial and the availability of male contraception agents may arrive within the next decade. For more information please follow the link to the Eunice Kennedy Shriver National Institute of Child Health and Human Development website (https://www.nichd.nih.gov/).

References

  1. Long JE, Lee MS, Blithe DL. Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods. Clin Chem 2019;65(1):153-160.
  2. Wang C, Page S, Nagia A, et al. Study of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception. https://clinicaltrials.gov/ct2/show/NCT03452111. Dec 11, 2019.
  3. Wu S, Yuen F, Swerdloff RS, et al. Safety and Pharmacokinetics of Single-Dose Novel Oral Androgen 11β-Methyl-19-Nortestosterone-17β-Dodecyl carbonate in Men. J Clin Endocrinol Med 2019; 104(3):629-638.
  4. Gava G, Meriggiola M. Update on male hormonal contraception. Ther Adv Endocrinol Metab. 2019;10.
  5. Glasier A. Acceptability of contraception for men: a review. Contraception 2010; 82(5):453-456.
  6. Roth M, Shih G, Ilani N, et al. Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial. Contraception 2014;90(4):407-412.
  7. Daniels K., Amba J. Current Contraceptive Status Among Women Aged 15–49: United States, 2015–2017. CDC. https://www.cdc.gov/nchs/products/databriefs/db327.htm. Accessed December 22 2019.
  8. Ghazal-Aswad S, Zaib-Un-Nisa S, Rizik DE, et al. A study on the knowledge and practice of contraception among men in the United Arab Emirates. J Fam Plann Reprod Health Care 2002; 28(4):196-200.
  9.  

Photo by Anna Shvets on Pexels.com


About the Author

Steven Gonzalez PharmD CandidateSteven Gonzalez, PharmD Candidate is a pharmacy student in the Chicago College of Pharmacy Class of 2022 at Midwestern University, with the dream of becoming a successful clinical pharmacist. In his time off, Steven enjoys spending time with his friends and family, going hiking, fishing, and watching classic movies.

Article reviewed by Brooke Griffin, PharmD, BCACP

Contraception During COVID-19: Pharmacy Best Practices

Pharmacists should not allow postponed or cancelled appointments to keep patients from accessing birth control. It’s important that patients understand how their pharmacy can continue to meet their contraceptive needs during the coronavirus disease 2019 (COVID-19) pandemic.

Pharmacists should inform patients that even though clinics and providers’ offices might be closed, their pharmacy is still able to facilitate refills, provide emergency contraception, and, in some states, prescribe hormonal contraception.

The following tips can help ensure your pharmacy is meeting patients’ contraceptive needs during COVID-19, while keeping your patients and pharmacy staff safe.

1. Encourage Contactless Communications and Dispensing 

Prevent patients from missing doses or going without contraception by preemptively contacting them via texts, emails, and calls to assess their needs. Encourage patients to utilize contactless communication to get in touch with the pharmacy for prescriptions or other items they want to order.

Pharmacies can provide contactless contraceptive care during COVID-19 by encouraging patients to obtain birth control prescriptions and products via mail, drive-through, or curbside pick-up services.


2. Promote and Supply Over-the-Counter Products

Visits to the pharmacy may be very limited for patients because of stay-at-home orders, social distancing, and other COVID-19-related barriers. Preemptively supplying prescriptions for emergency contraception can avert out of pocket costs while mitigating stress for patients that experience method failure and are unable to access the pharmacy in a timely manner.2 Encourage patients to have a pregnancy test on hand, in addition to over-the-counter contraceptive options, to ensure that patients’ contraceptive needs are met when routine visits to the pharmacy are not feasible.


3. Optimize Prescriptions and Anticipate Patient Needs

To maintain social distancing and the health of patients and employees, encourage providers to transmit new prescriptions electronically or via telephone.

Prescriptions for birth control should include maximum quantities and refills for a full year’s supply.2 Some states require health plans to cover dispensing a 12-month supply of birth control.3 Dispense the maximum amount allowed by the patient’s insurance and share the cash price if a patient desires paying out-of-pocket to limit visits to the pharmacy or clinic.

Pharmacy staff can proactively review patients’ profiles to anticipate upcoming refills and ensure the pharmacy’s birth control inventory is adequate to fulfill patient needs.

Check with your state’s COVID-19 pharmacy executive orders to ensure permitted emergency refills are being authorized.


4. Adapt Pharmacist Prescribing

Utilize Telehealth for Birth Control Visits

Patients are turning to telehealth services to access contraception during COVID-19. Transitioning your contraception service to telehealth wherever possible will ensure continuity of care while protecting the health and safety of patients and employees. Pharmacists can utilize telehealth to initiate contraception, assess and switch current methods, and adjust therapy as needed.

Due to COVID-19, some telehealth HIPAA regulations have loosened and health insurance plans are beginning to cover telehealth services.

Offer Methods that Don’t Require Blood Pressure Screening

Encourage patients to consider a progestin-only contraceptive if they’re unable to visit the pharmacy for a blood pressure screening.

Progestin-only contraceptive methods do not require a blood pressure screening in order to be safely prescribed, making them a feasible option when prescribing birth control via telehealth. Progestin-only options that can be prescribed by pharmacists and dispensed at the pharmacy include progestin-only pills (containing norethindrone or drospirenone) and depot medroxyprogesterone acetate injections (subcutaneous or intramuscular formulations).

Blood pressure measurement is required prior to initiating combined hormonal contraceptives—containing both estrogen and progestin hormones—due to the increased risk of stroke and myocardial infarction in patients with hypertension or without blood pressure measurements.

This article was co-written by Whitney Russell, a student pharmacist at University of Kentucky College of Pharmacy, and Kailey Hifumi, a student pharmacist at the Pacific University School of Pharmacy.

This article was originally published in Pharmacy Times.

Click image to view and download our COVID guide.

Find out more about providing contraceptive care during COVID-19 on our COVID resource page

References

  1. CDC. Guidance for pharmacies during COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/pharmacies.html; Published April 14, 2020. Accessed May 15, 2020.
  2. Family Planning National Training Center. What family planning providers can do to meet client needs during COVID-19. https://www.fpntc.org/resources/what-family-planning-providers-can-do-meet-client-needs-during-covid-19. Accessed May 15, 2020.
  3. Kaiser Family Foundation. Oral contraceptive pills. Available at: https://www.kff.org/womens-health-policy/fact-sheet/oral-contraceptive-pills/. Published May 23, 2019. Accessed May 15, 2020.
  4. Beyond the Pill. Contraceptive care during COVID-19. https://beyondthepill.ucsf.edu/contraceptive-care-during-covid-19. Accessed May 15, 2020.

Clinical Considerations for Contraception During COVID: Extended Duration of IUDs and Implants

Contraceptive care should not be compromised during this global pandemic. As many providers transition to contactless care methods via telehealth, patients that utilize long-acting reversible contraception may be worried if their intrauterine device (IUD) or implant has reached its expiration and needs to be removed or replaced. Pharmacists play an important role in educating patients about birth control, including what options are available to them when in-person appointments are not available at their regular clinic or doctor’s office. 

Expiration Dating 

The expiration date listed on the IUD and implant packaging should not be confused with the duration of use. The date stated on the packaging refers to the date by which the implant and IUD should be inserted.  Therefore, as long as the contraceptive device is inserted before the expiration date listed on the package, the IUD or implant will be effective for the entire duration indicated for each method. If the expiration date listed on the package has passed, the device is considered expired so it should not be used for a patient and should be discarded.  

Duration

Studies have demonstrated that IUDs and implants are effective past the FDA-approved duration. This evidence can help minimize concerns about ineffective devices that cannot be replaced due to cancelled doctor’s appointments due to COVID-19 or patient inability to go in due to exposure concerns, insurance loss, or any challenges. See table below to view extended evidence-based durations. 

Table modified from Reproductive Health Access Project

If the IUD or implant usage extends beyond the evidence-based duration, the patient should utilize an alternative birth control method until she is able to resume in-person visits with their provider to remove the device and possibly replace it with a new one if the patient desires. Providers should inform patients that leaving an IUD or implant in place past the evidence-based duration will not cause harm. While there are no safety concerns, there is no benefit as the device is not expected to be effective.

Pharmacists Roles

Pharmacists cannot prescribe or insert IUDs or implants, however, pharmacists have the ability to prescribe self-administered hormonal contraceptives in some states and can always provide over-the-counter barrier and emergency methods. If patients want an implant or IUD, pharmacists are able to initiate an alternative method in the meantime until patients are able to visit their clinic or doctor’s office for IUD or implant insertion. See our COVID page for more on providing contraceptive care during COVID-19. 

For patients not satisfied with their current birth control regimen who are interested in switching to an IUD or implant, pharmacists can refer the patient to a provider and educate the patient on proper bridging methods to prevent pregnancy during the transition to an IUD or implant. 

It is important that pharmacists stay up to date on birth control recommendations and clinical updates in order to provide guidance for patients and providers during a public health emergency. Pharmacists play an integral role in providing patients with the resources and education needed to make informed decisions on their contraceptive options. See the ACCP Women’s Health PRN Opinion Paper on the pharmacist’s role in safe and effective use of long-acting reversible contraceptive methods. 

If a patient is having symptoms related to their IUD or implant, they should be seen for this at a local clinic or doctor’s office. To find a clinic that provides contraceptive devices, visit Bedsider’s clinic finder.

References


About the Author

Kailey Hifumi is a student pharmacist at the Pacific University School of Pharmacy.

Photograph of Kailey Hifumi

5 Pearls from the 2020 States Forum on Pharmacist Birth Control Services

The second annual States Forum on Pharmacist Birth Control Services recently was held by the Birth Control Pharmacist project in partnership with the National Alliance of State Pharmacy Associations (NASPA). Due to the coronavirus disease 2019 (COVID-19) pandemic, this year’s meeting was held virtually as representatives from across the United States, as well as Canada, discussed advances in pharmacist birth control services.

Following a brief overview of the current landscape from the 2019 report, representatives shared updates on pharmacist birth control services in their respective states. The implementation status among the states ranged from fully implemented, in progress, and under consideration, to not being considered at this time.

Each representative was able to provide insight on their successes, challenges, and tips on obtaining state-wide authorities to provide contraception services. Attendees also participated in breakout sessions to brainstorm ideas to improve public awareness, research and evaluation, payment for pharmacist services and advance policy.

Here are 5 pearls to take away from the 2020 States Forum:

  1. Exercise authorities granted by emergency regulations due to COVID-19. As the global pandemic continues to unfold, many states are allowing pharmacists to dispense emergency refills and extended supply quantities. This provision includes refills for hormonal contraception. This unique circumstance can highlight the benefits of implementing contraceptive services within the pharmacy and pave the way for expanded access to birth control.
  2. Identify champions to build a coalition for planned policy proposals. A common barrier expressed in the states forum was legislation halts due to COVID-19. It is important to use this time as an opportunity to expand our outreach to pharmacists and physicians to gain support on pharmacist contraceptive services in the meantime. By identifying pharmacist and physician champions to reach out to medical associations and organizations, states can hopefully overcome and alleviate apprehension from groups opposed to proposed legislation. By educating pharmacist colleagues of the value of providing these services and providing educational resources, we can mitigate pharmacist opposition to legislation. Consider reaching out to obstetrician-gynecologist colleagues, particularly those who are members of the American College of Obstetricians and Gynecologists or have completed a family planning fellowship, to aid in coalition building and policy planning for pharmacist birth control services.
  3. Encourage fellow pharmacists to partake in providing contraceptive services. Pharmacists are key health care members and well equipped to provide these clinical services. There are currently more than 3000 participating pharmacies on the Birth Control Pharmacies map. However, there is still room to expand our reach to more communities as pharmacists. Many pharmacy schools have, or are in the process of implementing, curriculum to complement the implementation of birth control services within pharmacies throughout the US. In some states, legislation has grandfathered pharmacy school graduates to remove additional training barriers. Encourage your colleagues, preceptors, and teams to complete continuing education on contraception services, particularly if practicing in a state with a protocol or other authority available that allows pharmacists to prescribe contraception.
  4. Promote pharmacy services on different platforms to raise public awareness. Although a handful of states have implemented pharmacist birth control services, patients remain widely unaware. By promoting this pharmacy service via signs, social media platforms, partnerships, and through word of mouth, we can expand our impact within the community. Seek partnerships with local student pharmacists and student pharmacy organizations to further promote birth control services.
  5. Join the next States Forum on Pharmacist Birth Control Services. This forum is an opportunity to participate in valuable discussion, and share experiences and strategies to advance pharmacist contraception services in your state. This session was especially helpful for states that are in the process of, or are considering, pharmacy birth control legislation.

If you missed the 2020 States Forum, you may view the meeting recording.

Join the Birth Control Pharmacist email list to be notified of details for the next States Forum. 

The Birth Control Pharmacist project was established to provide training and education, implementation assistance, resources, and clinical updates for pharmacists prescribing contraception. Beyond service implementation, this project engages in advocacy, research and policy efforts within the community to expand the role of pharmacists in family planning.

The mission of NASPA is to provide support and to facilitate collaboration between state pharmacy associations to advance the profession of pharmacy.

This article was co-written by Kailey Hifumi, a student pharmacist at the Pacific University School of Pharmacy.

This article was originally published in Pharmacy Times.

Contraception During COVID: California’s Medi-Cal and FamilyPACT Programs Cover Depo-SubQ Provera

We recently wrote about the importance of offering patients subcutaneous depot medroxyprogesterone acetate (DMPA-SQ) as a contactless form of contraception during the COVID-19 public health emergency. California pharmacists can prescribe DMPA-SQ under statewide protocol upon completing the required training program and obtain payment for the visit for Medi-Cal patients.

As of April 9, 2020, California’s Medi-Cal, FamilyPACT, and managed Medi-Cal health plans are covering DMPA-SQ under pharmacy benefits.

To facilitate compliance with state and federal guidelines for sheltering in place and physical distancing, DHCS will temporarily allow for pharmacy dispensing of DMPA-SQ directly to patients for self-administration at home. This is in addition to current Medi-Cal policy that allows administration by a health care professional. Self-administration of DMPA-SQ would be at the option of the Medi-Cal recipient after individualized discussions and decision-making between the prescriber and the recipient. The prescribing provider is responsible for ensuring proper training of the recipient in administering the drug, potential side effects, and proper disposal of the pre-filled syringe.

The FamilyPACT system updates to allow for claim reimbursement of DMPA-SQ will not be implemented until May 15, 2020 for pharmacy dispensing, with a retro-effective date on or after April 9, 2020.  Pharmacies may re-process their denied claims after the implementation date and it should process successfully at that time. FamilyPACT always recommend that pharmacies validate eligibility, process the claim, get the denial, dispense the medication, and reprocess the claim after May 15 for payment. The reprocessed claim will show payment for the actual date of service as long as it is not before April 9.

Additionally, a reminder that a Medi-Cal beneficiary should not be required to pay for a covered medication until all avenues of successful processing have been explored and the department denies the service (for example the provider tries obtaining a TAR) and only if the patient requests to purchase the medication out of pocket. 

The full policy document is published on the COVID-19 webpage at: Direct-to-Patient Dispensing of Subcutaneous Depot Medroxyprogesterone Acetate – COVID-19 Emergency. This temporary policy change is effective immediately and remains in effect until further notice.

Clinical Considerations for Contraception During COVID: Patient Self-Administration

During the COVID-19 pandemic and beyond, patients may desire a contactless method of contraception. The subcutaneous (SQ) formulation of depot medroxyprogesterone acetate (DMPA), Depo-SubQ Provera, is an important option to offer patients. This may be of particular interest among patients who currently come in to the pharmacy or go to a clinic for their intramuscular (IM) injection.

Formulation Differences

While patients are able to self-administer both subcutaneous and intramuscular injections for a variety of purposes (e.g., insulin, fertility medications), patients may prefer the SQ formulation of DMPA since it is associated with less pain and higher continuation rates than the IM formulation.

Differences between the two formulations are summarized in the table below.

Intramuscular (IM)Subcutaneous (SQ)
Dose150 mg104 mg
Duration13 weeks
(up to 15 weeks)
12-14 weeks
Generic AvailabilityYesNo
Cost at Pharmacy$70-100>$200

Another important consideration is insurance coverage of these products. Some health plans cover the IM formulation as a medical benefit but have not yet included it as a pharmacy benefit. Some health plans are now covering the SQ formulation as a pharmacy benefit due to COVID-19, while others cover it as a pharmacy benefit but require a prior authorization.

How to Initiate or Switch

There is no physical assessment or blood pressure measurement required for eligibility of DMPA.

If your patient is not currently using a method of hormonal contraception, they can begin using either the IM or SQ at any time during the menstrual cycle if it is reasonably certain that patient is not pregnant. A backup method of contraception should be used for 7 days.

If your patient is currently using IM DMPA, the SQ DMPA can be administered when she is due for her next injection. No backup contraception is needed.

If your patient is currently using any other hormonal contraception (i.e., progestin only-pill, hormonal IUD, combination hormonal pill, patch or ring) or a copper IUD, the DMPA should be administered 7 days before stopping the other method. No backup contraception is needed.

References

2020 CDC Update for Contraceptive Use in Women at High Risk for HIV

What is the significance?

Women who have unprotected sex or have multiple partners have not only an increased the risk of sexually transmitted infections (STIs also known as STDs) but also have a risk of pregnancy. Aside from condoms, other contraceptive methods do not protect against HIV and other STIs but can effectively prevent an unintended pregnancy with potential complications and perinatal transmission associated with HIV infection.  Based on the new 2019 recommendations by the World Health Organization (WHO), the CDC published updated guidelines to the 2016 U.S. Medical Eligibility Criteria (US MEC) for Contraceptive Use regarding women at high risk for HIV infection in April 2020.

 

What changed?

The following updates were made to the US MEC for Contraceptive Use, 20161:

Women at high risk for HIV:

There are no restrictions for use (MEC Category 1) of all contraception methods, now including IUDs and depot medroxyprogesterone acetate (DMPA) injection. Previously, high risk for HIV was a condition for which copper-containing and progesterone-releasing IUD and DMPA use was MEC Category 2 (benefits generally outweigh the risks of the condition).

Women on antiretroviral (ARV) therapy:

The CDC has clarified that their recommendations for contraception in women taking nucleoside reverse transcriptase inhibitors (NRTIs) applies to all NRTI indications: prevention (PrEP) or treatment of HIV infection. Most contraceptive methods are MEC Category 1 except initiation of IUDs in women whose HIV viral loads are not controlled or are not ARV therapy due to the risk of pelvic inflammatory disease due to the risk of pelvic inflammatory disease with IUD insertion (MEC Category 2).

See Table 1 for a summary of recommendation changes.

 

Summary of Clinical Evidence

The US MEC recommendations are based on a review of clinical evidence, the WHO recommendations, and epidemiological information regarding unintended pregnancy, contraceptive use, HIV infection, and maternal morbidity and mortality in the US.2 In the previous 2017 US MEC update, intramuscular DMPA (DMPA-IM) use changed from a category 1 to a category 2 based on evidence of possible increased risk for HIV acquisition in women using DMPA who are already at high risk of infection.2,3 However, in August 2019, the WHO published the following updates regarding recommendations for contraceptive use in this population:

Women with high HIV risk are eligible to use all methods of contraception without restriction (category 1)4

    • All progestin-only methods, including progestin-only pills (POPs), intramuscular and subcutaneous DMPA, levonorgestrel (LNG) implants, and etonogestrel (ETG) implants
    • Copper and LNG intrauterine devices (IUDs)
    • All combined hormonal contraceptive methods, including combined oral contraceptives (COCs), combined contraceptive patches, and combined vaginal rings

These recommendations for this patient population have been made in light of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, which aimed to determine the risk of HIV incidence with the use of DMPA-IM, copper IUD, and LNG implant contraceptives. The randomized, multicenter, open-label trial included 7,839 non-pregnant, HIV-seronegative African females aged 16 to 35 years seeking effective contraception who were placed into 3 groups of contraceptive methods: DMPA-IM, copper IUD, and LNG implant.3 After 18 months, 397 HIV infections were observed: 36% in the DMPA-IM group, 35% in the copper IUD group, and 29% in the LNG implant group with no significant statistical differences between each method.3 Therefore, DMPA-IM copper IUD, or LNG implant use does not further increase the risk of getting HIV in patients already at high risk for HIV. In addition, patients younger than 25 years were associated with higher HIV incidence than those 25 years or older, and herpes simplex virus-2 (HSV-2) seropositive patients were associated with higher HIV incidence than those who were HSV-2 seronegative.3 However, age and HSV-2 status did not significantly alter the relationship between contraceptive use and HIV acquisition.3

Although the ECHO trial did not assess other hormonal methods (e.g., COCs, subcutaneous DMPA, hormonal IUDs), WHO also made their recommendations based on low/low-to-moderate quality studies or extrapolation from other studies indicating no increased risk for HIV acquisition with these methods.3,4 A consensus was also made that “no biological or clinical reasons” were evident “that a lower hormonal dose, different delivery mechanism, or different progestin” would affect HIV risk.”3

 

References

  1. Tepper NK, Curtis KM, Cox S, Whiteman MK. Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection. MMWR Morb Mortal Wkly Rep 2020;69:405–410. Available from:http://dx.doi.org/10.15585/mmwr.mm6914a3
  2. Tepper NK, Krashin JW, Curtis KM, et al. “Update to CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Revised Recommendations for the Use of Hormonal Contraception Among Women at High Risk for HIV Infection.” MMWR Morb Mortal Wkly Rep. 2017;66(37):990-994.
  3. Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet. 2019;394(10195):303-313.
  4. Contraceptive eligibility for women at high risk of HIV. Guidance statement: recommendations on contraceptive methods used by women at high risk of HIV. Geneva: World Health Organization; 2019. License: CC BY-NC-SA 3.0 IGO.

Marjorie Valdez Student PharmacistAbout the Authors

Marjorie Valdez is a fourth-year pharmacy student at the UC San Diego School of Pharmacy and Pharmaceutical Sciences.

Cydnee Ng, PharmD completed her pharmacy training at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences in 2019. She is currently a community pharmacist at Walgreens in the San Francisco Bay Area.

Contraception for Your Transgender Patients

Terminology

Navigating through a discussion about gender and sexuality with the many terms used today can be confusing. Here is a brief introduction to terminology regarding the multifaceted gender spectrum.1

  • Cisgender: Gender identity matches assigned gender at birth2
  • Transgender: Gender identity differs from assigned gender at birth2
  • Gender nonbinary/queer/fluid: Individuals do not identify with a male-female binary and may have a fluid, multifaceted gender identity2

Now let’s review contraception for transgender patients…with a focus on transgender men (male gender identity and female assigned gender at birth)…

Considerations for contraception care

Gender affirmation therapy does not take the place of contraception.

Each patient may prefer different gender affirmation methods, which may affect their contraceptive needs.Methods include hormone therapy with testosterone, surgery, or no intervention. For patients undergoing testosterone therapy or no intervention who desire contraception, an additional contraceptive method becomes necessary. On the other hand, patients who undergo reaffirming surgery may or may not need additional contraception to reduce risk of pregnancy, depending on the extent of surgery performed.

 

There are knowledge gaps around fertility and contraceptive needs amongst transgender patients and their providers.

Some transgender men and providers have a lack of knowledge regarding their reproductive potential and risk of pregnancy if sexually active with a capable partner.3 Misperceptions include testosterone as effective contraception (may decrease fertility, but does not eliminate pregnancy risk) and midlife patients as infertile (presumed menopausal).3,4,5

 A transgender man has reproductive potential if they have an intact uterus and ovaries and until menopause or surgical sterilization.3 In addition, testosterone use may not completely suppress ovarian function, causing irregular or suppressed periods, which should not be confused with perimenopause in midlife patients.3,5 It is important to note there is still a risk of pregnancy despite a lack of menstruation. In a study of 41 transgender men who had been pregnant and given birth, one-third of pregnancies were unintended.Contraception use prior to pregnancy was lower in patients who used testosterone compared to those who did not.6 Use of a contraceptive is still necessary even with testosterone therapy.

 

Transgender patients have barriers to care that may prevent provision of adequate sexual and contraceptive care

Examples of barriers include stigmatization and feeling unsafe in health care settings.Health care teams should provide a supportive, open, and safe environment for transgender patients by accepting their gender identity and sexual orientation and using their preferred name and pronouns. Providers should ask if patients have an intact uterus and ovaries, are sexually active with a partner that may result in pregnancy, have a history of sexual violence, are at risk of sexually transmitted infections (STIs), and use gender affirmation methods.3

 

There is a lack of research on pregnancy risk and fertility in transgender patients, and consequently, contraceptive guidelines for this patient population.3

 

Contraception for transgender men

All transgender men with reproductive potential should be offered contraception.5 Patients should decide which contraceptive they prefer to use, if any. 

 

Reversible contraceptives

Reversible methods are most appropriate for patients who have not decided or do not want to make long-term or irreversible decisions regarding their reproductive potential.3

 

Progestin-only contraceptives

Progestin-only methods do not interfere with testosterone use. Regardless of testosterone use, patients who continue to have menstrual cycles may prefer this method due to high rates of amenorrhea and potential for masculinizing effects (e.g., increased hair growth).5,7

Traditional progestin-only pills (POP) containing norethindrone have a risk of low patient adherence due to its strict 3-hour window, which by missing correct timing of doses, may compromise contraceptive efficacy.However, the new POP, Slynd, allows for a 24-hour missed pill window.9 Irregular bleeding may occur, which patients may want to avoid.8

For patients seeking longer acting methods, the progestin-only injectable and long-acting reversible contraceptive devices — implant and IUDs — may be more convenient and have higher rates of amenorrhea.

 

Combination hormonal contraceptives

There is a lack of evidence regarding combined hormonal contraceptives including pills, patches, and vaginal rings) for transgender men as the estrogen may or may not interfere with testosterone therapy. At this time, there are no contraindications to concurrent use.5 Though patients can choose combination hormonal contraceptives, some may not prefer this method due to concerns about having estrogen in their system and the potential for female traits to appear.5,10 Other available and acceptable methods should be considered before considering combination hormonal contraceptives.5

 

Nonhormonal contraceptives

Although the copper IUD does not interfere with testosterone, there is a risk of increasing any existing menstrual bleeding.5 Patients with an intact uterus who want to avoid both progestins and estrogens and who are already amenorrheic may prefer this method.5

The contraceptive effectiveness of external and internal condoms is lower than hormonal methods and LARCs, however they are essential to prevent HIV and other STDs.3

Permanent surgical options are available for patients who do not want to get pregnant at all.3,7

 

Contraceptives for transgender women

For patients with a female gender identity and male sex assigned at birth taking estrogen, condoms may be used as well as permanent options, including orchiectomy (removal of testicles) and vasectomy (blockage of vas deferens tubes, preventing sperm from reaching testicles).7

 

For more information regarding transgender care and terminology, please visit the UCSF Transgender Care Navigation Program website at transcare.ucsf.edu/guidelines.

 

References

  1. Justice for Sisters. “Update: Gender Bear Now in BM, Chinese Language & English.” Accessed on September 5, 2019. Available at: https://justiceforsisters.wordpress.com/2016/07/13/updated-gender-bear-in-bm-chinese-language-english/.
  2. UCSF Transgender Care Navigation Program. “Terminology and definitions.” UCSF Transgender Care Navigation Program. June 17, 2016. Accessed on September 11, 2019. Available at: https://transcare.ucsf.edu/guidelines/terminology.
  3. Francis A, Jasani S, Bachmann G. Contraceptive challenges and the transgender individual. Womens Midlife Health. 2018;4:12.
  4. Amato P. “Fertility options for transgender persons.” UCSF Transgender Care Navigation Program. June 17, 2016. Accessed on September 11, 2019. Available at: https://transcare.ucsf.edu/guidelines/fertility.
  5. Boudreau D, Mukerjee R. Contraception care for transmasculine individuals on testosterone therapy. J Midwifery Womens Health. 2019;64(4):395-402.
  6. Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120-1127.
  7. Shah M. “Birth control across the gender spectrum.” Bedsider. 2017. Accessed on September 11, 2019. Available at: https://www.bedsider.org/features/1070-birth-control-across-the-gender-spectrum.
  8. Jones K, Wood M, Stephens L. Contraception choices for transgender males. J Fam Plann Reprod Health Care. 2017;43(3):239-240.
  9. Exeltis USA, Inc. “Exeltis USA, Inc. announces the approval of Slynd, the first and only progestin-only pill providing pregnancy prevention with a 24/4 dosing regimen and 24-hour missed pill window.” Exeltis USA, Inc. June 6, 2019. Accessed on November 19, 2019. Available at: https://www.prnewswire.com/news-releases/exeltis-usa-inc-announces-the-approval-of-slynd-the-first-and-only-progestin-only-pill-providing-pregnancy-prevention-with-a-244-dosing-regimen-and-24-hour-missed-pill-window-300863390.html.
  10. Reproductive Health Access Project. “Birth control across the gender spectrum.” Reproductive Health Access Project. 2019. Accessed on September 11, 2019. Available at: https://www.reproductiveaccess.org/wp-content/uploads/2018/06/bc-across-gender-spectrum.pdf
  11.  

About the Author

Cydnee Ng, PharmD completed her pharmacy training at UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences in 2019. She is currently a community pharmacist at Walgreens in the San Francisco Bay Area.

Twirla: A New Contraceptive Patch

What is Twirla?

Twirla is a new contraceptive patch designed for patients who want freedom from the daily pill without committing to a longer acting method. This transdermal patch delivers 120mcg of levonorgestrel and 30mcg of ethinyl estradiol through Agile’s Skinfusion® patch, which consists of five layers and serve as the reservoir for the active and inactive ingredients, as well as a barrier to prevent accumulation of debris from daily wear. Twirla is designed to be applied once weekly for three weeks, followed by one patch free week for menstruation.

Currently there is only one hormonal contraceptive patch available for consumer use called Xulane (norelgestromin 150mcg/ethinyl estradiol 35mcg). Women who use this patch have higher blood serum concentrations of estrogen compared to oral methods (AUC0-∞ 37.7±5.6 vs. 22.7±2.8), which is associated with health concerns such as increased risk of blood clots in the legs and lungs. Agile Therapeutics, the women’s healthcare company behind Twirla, saw an unmet need in the market for a low-dose hormonal contraceptive patch. This market gap lead to the development of their newly formulated contraceptive patch, Twirla.

 

What are the pros and cons of Twirla?

This patch provides another option for women who desire an alternative from a daily pill, without the constraints of a longer acting method. Twirla is applied once weekly, meaning women only have to remember their birth control about three times a month rather than every day. With various daily activities and responsibilities, a weekly patch liberates women from one of those daily routines. There are other birth control options such as the Depo-Provera injection, IUDs, or implants that serve as alternatives to the pill but some women perceive these methods as more invasive compared to the patch. Additionally, given the lower dose of estrogen, Twirla appears to have a lower risk of blood clots as shown in comparator studies but remains equally effective in regulating menstrual cycles and preventing pregnancies as compared to the existing patch option.

Although the convenience of a patch is desirable, there are several noteworthy considerations with this product. As previously mentioned, Twirla’s formulation lowers the risk of blood clots, but there remains a risk of blood clots with hormonal patches compared to oral methods.  Additional side effects reported with Twirla include unscheduled vaginal bleeding, weight gain, headache, and abdominal cramps.  Women have also reported skin irritation when applying and removing the patch. Regarding size, Twirla is round and slightly larger (28cm2) than the Xulane (14 cm²) patch. Additionally, both Twirla and Xulane are currently only produced in one neutral shade of beige. For many women, this prevents the possibility of a discrete form of birth control which may make this a less desirable option.

 

Are there different considerations with a patch compared to other contraceptive methods?

Given the hormones in Twirla, the patch works just like the pill in terms of preventing pregnancy by delaying ovulation.  It can be applied on the upper arm, buttocks, back, or lower abdomen. The patch is designed to withstand activities such as exercising, swimming, showering, etc. If the patch does happen to fall off during the week, it can be reapplied or a new patch may be used in its place. If the patch has been off more than 24 hours, a back up method such as condoms should be used for the next seven days of the new patch cycle. Although it’s rare (<2% of the time), healthcare providers recommend daily checks to ensure the patch has not accidentally fallen off. Patches should not be worn longer than the week they are intended and consequences of doing so include bleeding, spotting, and increased risk for unintended pregnancy. If a patient is more than 48 hours late transitioning from the existing patch to a new patch, then a back up should be used for seven days. Like all other birth control methods, Twirla does not protect against sexually transmitted diseases or HIV.

 

Is Twirla a good option for everyone?

There is no one-size fits all method that is right for all women. Some women might be at greater risk for adverse effects with the patch. Agile reported reduced efficacy in preventing pregnancy for women who weigh 202 pounds (92kg) or more, or who have a BMI of 30 kg/m2 or greater. As a result, the drug company initially issued a Limitation of Usestatement in their product labeling that documented this clinical outcome.  Since gaining FDA approval, this limitation has transitioned to a listed contraindication. Xulane’s package insert lists the same contraindication, yet is regularly prescribed in women with a BMI >30 kg/m2. Studies have shown that the decrease in efficacy does not preclude the use of these patches in obese women. To combat the associated risks, additional counseling to emphasize the importance of strict compliance with the patch for optimal protection is necessary. Studies have also shown an increased risk in blood clots in women who are overweight and those who smoke. Additional contraindications for using Twirla include women with a high risk of thrombotic disease, who experience migraine with aura, who have liver disease, or who have undiagnosed abnormal uterine bleeding.

 

Is Twirla available now?

Twirla was approved by the FDA earlier this month on February 14, 2020. As part of the approval process, the FDA is requiring Agile to conduct a long term, observational post-marketing study to further evaluate the risks of blood clots in new users of Twirla. With its recent approval, the manufacturer is now focusing their attention on commercializing Twirla for consumer use. They hope to complete the manufacturing process and expect to ship the initial product to wholesalers as early as the end of this year.

With patient needs and safety in mind, the approval of this medication further expands the range of contraceptive options available for women. Given that there have only been three non-daily combined hormonal contraceptive methods made available since 2001, this is a valuable and timely option for women who seek alternative methods.

References

  1. FDA Approves Agile Therapeutics, Inc.’s Twirla® (levonorgestrel and ethinyl estradiol) Transdermal System – A New Weekly Contraceptive Patch Delivering a 30 mcg Daily Dose of Estrogen and 120 mcg Daily Dose of Progestin. (2020, February 14). Retrieved February 23, 2020, from https://ir.agiletherapeutics.com/news-releases/news-release-details/fda-approves-agile-therapeutics-incs-twirlar-levonorgestrel-and
  2. Efficacy, Safety and Tolerability Study of Agile AG200-15 Transdermal Contraceptive Delivery System – Full Text View. (2017, September 25). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02158572?term=AG200-15&draw=2&rank=1
  3. Therapeutics, A. (n.d.). Results From the SECURE Trial, a Phase 3 Study of the… : Obstetrics & Gynecology. Retrieved from https://journals.lww.com/greenjournal/Abstract/2017/05001/Results_From_the_SECURE_Trial,_a_Phase_3_Study_of.46.aspx
  4. Hatcher, R. A. et. al (2018). Contraceptive technology. New York, NY: Ayer Company Publishers, Inc.
  5. Van den Heuvel et. al, M. W. (2005). Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception72(3). Retrieved from https://www-sciencedirect-com.proxy-remote.galib.uga.edu/science/article/pii/S0010782405000971 

About the AuthorBirth Control Pharmacist Headshots

Savannah Gross is a third-year pharmacy student at the University of Georgia College of Pharmacy. 

Article reviewed by Rebecca Stone, PharmD, BCPS, BCACP

Endometriosis Basics and How Contraception Can Help

What is endometriosis?

Endometriosis is characterized as a condition in which endometrial tissue, which normally lines the uterus, develops outside of the uterine cavity in abnormal locations such as the ovaries, fallopian tubes and abdominal cavity.1 Endometriosis is a common cause of chronic pelvic pain in women and can sometimes be associated with infertility.2 It is estimated that 1 in 10 women suffer from endometriosis (with percentages even higher in women with chronic pelvic pain and infertility).  On average, it takes anywhere from 3 to 11 years from the onset of pain symptoms for women to be accurately diagnosed with endometriosis.3

As pharmacists, it is important to establish our role in patient care and to be aware of this underdiagnosed condition and the role of hormonal contraception in managing symptoms and the disease. We can assist patients with endometriosis by having confidence in the medication they were prescribed and keeping in mind the individual treatment goals in each patient. While there is no definitive cure for endometriosis, there are pharmacological approaches in the management of the associated pain. While there are many different options available for women with endometriosis, this article will be focusing on the use of hormonal contraceptives in endometriosis pain management. Additionally, it is important to keep in mind that no hormones are free of side effects and severity and tolerability can vary significantly; not all types of endometrial pain respond equally to hormonal treatment.4

 

What is the role of hormonal contraceptives in endometriosis treatment?  

Combined hormonal contraceptives (CHCs) and progesterone only pills (POPs) have been used for pain management associated with endometriosis. Hormonal contraceptives help to slow the growth of new endometrial tissue and may prevent formation of new adhesions which can help decrease the pain patients have. However, hormonal contraceptives will not eradicate any endometrial tissue that currently exists in the patient.5

There are a few differences in tolerability and the level of evidence for each treatment. For assessing the different types of contraceptive treatment for endometriosis, the European Society of Human Reproduction and Embryology (ESHRE) has created a grading scale as part of their justification for treatment:

Grading Scale

Grade A: treatment has been backed by meta-analysis, systemic review or multiple RCTs (high quality). 

Grade B: treatment has been backed by a meta-analysis, systemic review or multiple RCTs (moderate quality), single RCT, large non-randomized trial, case-control or cohort studies (high quality). 

Grade C: treatment has been backed by a single RCT, large non-randomized trial, case-control or cohort studies (moderate quality).4

CHCs may considered as it can reduce endometriosis-associated dyspareunia, dysmenorrhea and non-menstrual pain.4 Oral CHCs are considered “Grade B”.4 It is important to note that endometriosis is considered to be a predominantly estrogen-dependent disease. It is possible that the estrogen component of CHCs may mask the effect of the progestin by possibly activating the disease. However, it has been argued that ethinylestradiol doses are too low to reach an activating threshold.4 According to the American College of Obstetricians and Gynecologists (ACOG) guidelines, CHCs showed significant decrease in pain in patients and if that therapy is not tolerated patient could move on to progestins. Unlike the ESHRE, they did not differentiate between types of contraceptives and their related effectiveness.5 

Among the CHCs, it is important to recognize that different dosage forms have different grades of evidence of efficacy in the ESHRE guidelines. Continuous CHCs (active tablets only) were given a “Grade C”.  Vaginal contraceptive rings and transdermal patches were also given a “C”.4

Progestin-only pills are considered “Grade A” by the ESHRE guidelines because they have the most evidence to date in reducing endometriosis-related pain. Additionally, while Levonorgestrel-containing IUDs are not FDA approved as treatment for endometriosis, they are given a “Grade B” as an option to reduce pain related to the disease.4 Additionally, the ACOG guidelines recognize the use of levonogersterol-containing IUDs to reduce endometriosis related pelvic pain, but emphasized that potential side effects like irregular bleeding and weight gain are common.5  

Another type of progestin contraceptive that can be used for endometriosis-associated pain is Depot medroxyprogesterone (DMPA). DMPA works to prevent follicular growth preventing ovulation.6 ACOG recognizes DMPA as a suitable treatment as it has been approved by the FDA for treatment of endometriosis-associated pain.5 Furthermore, ESHRE gave DMPA a “Grade A” as an option to reduce endometriosis-related pain.4

As pharmacists, we serve a vital role in the patient care plan and can be there to help patients recognize the types of treatment options available to them. As a patient, it may be hard navigating through the different contraceptive options that they have for endometriosis pain management. Pharmacists can help patients navigate these options in order to help improve their quality of life.

References

    1. Noncontraceptive benefits of birth control pills: fact sheet. ASRM (American Society for Reproductive Medicine). Available from: https://www.reproductivefacts.org/globalassets/rf/news-and-publications/bookletsfact-sheets/english-fact-sheets-and-info-booklets/noncontraceptive_benefits_of_bcp_factsheet.pdf. Accessed January 16, 2020
    2. Leyland N, Casper R, Laberge P, Singh SS, SOGC. Endometriosis: diagnosis and management. J Obstet Gynaecol Can 2010;7 (Suppl 2):S1–32.
    3. Husby GK, Haugen RS, Moen MH. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand. 2003;82(7):649–53. 
    4. Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et, al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-12.
    5. Committee on Gynecologic Practice. ACOG Practice Bulletin No. 114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–36.
    6. Depo-Provera CI (medroxyprogesterone acetate) [package insert]. U.S Food and Drug Administration website. Revised October 2010. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020246s036lbl.pdf. Accessed February 10, 2020

About the Author

Breanna HeadshotBreanna Failla, PharmD Candidate is in her second year of pharmacy school at Midwestern University Chicago College of Pharmacy. She serves as APhA-ASP Chapter President and Midyear Regional Meeting Coordinator for Region 4. 

Article reviewed by Brooke Griffin, PharmD, BCACP