Opill: The First FDA-Approved OTC Birth Control Pill

 Krista Anderson-Ross, ND | August 1, 2023

According to a committee opinion published by the American College of Obstetrics and Gynecology (ACOG) in 2021, barriers to access are one reason for inconsistent or nonuse of contraception. On Thursday July 13, 2023, the FDA approved Opill - a daily oral contraceptive pill for use without a prescription. Unlike the popular combination pill which contains a progestin and estradiol, the Opill contains only one hormone: .075mg of the progestin norgestrel. Research indicates that unlike combination pills, progestin-only pills do not increase the risk for high blood pressure or cardiovascular disease. Additionally, the progestin-only pill is considered safe to use with cardiovascular diagnoses such as deep vein thrombosis and uncontrolled high blood pressure.  

According to the FDA, norgestrel was approved for prescription use in the U.S. for prevention of pregnancy in 1973 but has not been available in oral form since 2005. The last iteration of the progestin-only pill, the “mini-pill;” also contained .075mg of norgestrel and was a continuous use pill with no placebos to be used throughout bleeding. The Opill is the same formulation with a new name. 

Perfect vs Typical Use 

In clinical trials, when taken at the exact same time every day without breaks between monthly packs, the Opill effectiveness rate is 98%. This is called “perfect use.” Perfect use also includes using back-up birth control when a pill is missed or delayed by more than 3 hours. Perfect use is what is seen in clinical trials. 

In clinical trials there is also the term “typical use,” to describe how a birth control pill is used in real life. Typical use encompasses human error such as forgetting to take a pill at the exact same time every day, or not using a back-up contraceptive method when a pill is missed. For these reasons the FDA expects typical use to be less effective than perfect use with a 91% effectiveness rate. This is due to the rapid distribution and elimination of norgestrel – after reaching maximum serum levels, the concentration decreases with a mean elimination half-life of 36+/-13 hrs. 

Mechanism of Action (MOA) 

There are several mechanisms of action of the norgestrel oral pill: 

  • Progestin causes cervical mucous to thicken creating a “plug” thereby reducing sperm viability and penetration. 
  • Progestin thins the lining of the uterus. 
  • Progestin can interfere with ovulation - norgestrel binds to progesterone and estrogen receptors in the reproductive tract, mammary gland, hypothalamus and pituitary thus lowering mid-cycle LH and FSH peaks. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy. 
  • Note: According to ACOG, ovulation inhibition is inconsistent as 4 in 10 women will continue to ovulate. 

Contraindications: 

  • Known or suspected pregnancy 
  • Known or suspected carcinoma of the breast or another progestin-sensitive cancer, currently or in the past 
  • Lupus 
  • Undiagnosed abnormal uterine bleeding 
  • Hypersensitivity to any component of the product ingredients (including FD&C Yellow No. 5) 
  • Benign or malignant liver tumors 
  • Acute liver disease 
  • May be less effective in women who are overweight or have obesity 

Warnings:  

The following are warnings from the Opill product monograph: 

  • Ectopic pregnancy – Incidence of ectopic pregnancy in progestin-only oral contraceptive users is 5 per 1000-woman years (1:200). Health-care providers should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on Opill tablets. 
  • Delayed follicular atresia/ovarian cysts – If follicular development occurs, atresia of the follicle can be delayed causing the follicle to continue to grow beyond the size it would in a normal cycle. Generally, these enlarged follicles disappear spontaneously. 
  • Bleeding Pattern Alterations – Irregular menstrual patterns are common in users. In the 8 US clinical trials of Opill tablets in 2,575 subjects, approximately half of them experienced “menstrual changes” including breakthrough bleeding (48.6%) and spotting (47.3%). Amenorrhea occurred in 6.1% of subjects in their first cycle and 28.7% of all subjects during the studies. Of the participants who discontinued treatment due to side effects, 67.6% claimed that it was due to irregular bleeding. Overall, 6.4% of participants discontinued treatment due to breakthrough bleeding and 2.7% due to amenorrhea.  
  • Hepatic neoplasia/liver disease – Recommended to discontinue Opill if jaundice or disturbances of liver function develop, not to resume until markers return to normal. 

*Drug/Herb Interactions: 

  • Medications for seizures, TB, HIV/AIDS, pulmonary hypertension    
  • St John’s Wort – this herb induces CYP3A4 metabolism and may reduce serum levels of norgestrel 
  • Grapefruit products – can inhibit CYP3A4 metabolism which may increase the serum concentration of norgestrel  

*for a more detailed list of drug interactions see: https://www.drugs.com/druginteractions/norgestrel,opill.html 

 

Opill and Mental Health: 

A growing body of research is linking hormonal contraception and potential adverse effects on women’s emotional health. A large Danish prospective cohort study of one million women found an association between an increased rate of depression in all hormonal contraceptive users, with worse outcomes in progestin-only pill users, especially in the 15-19 age demographic. Whereas users of combined oral contraceptives experienced a 1.8-fold higher rate of first use of antidepressants one year after commencing oral contraception, users of progestin-only pills experienced a 2.2-fold higher rate than controls. Given these statistics and the worsened state of mental health among youth post-COVID, providers may first recommend other forms of birth control in this young demographic, especially when mental health diagnoses are present. See this DDI newsletter article for more information on the link between declining mental health and nutrient depletion by hormonal contraception.

Testing Options: 

When using combination oral contraceptives that include estradiol, sex hormone binding globulin (SHBG) is increased which can bind estrogen and testosterone levels, making saliva testing less helpful as all hormone levels tend to be suppressed. In contrast, oral norgestrel has been shown to lower SHBG, and ovulation has been shown to take place close to 50% of the time, making saliva testing a consideration to evaluate estradiol, progesterone and testosterone levels in this population. Because of the potential for progestin-only oral contraception to impact mental health in youth, urinary neurotransmitter testing may also be a consideration for this population.  


 

References


https://www.fda.gov/news-events/press-announcements/fda-approves-first-nonprescription-daily-oral-contraceptive 

https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/opill-0075mg-oral-norgestrel-tablet-information  

https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2019/10/over-the-counter-access-to-hormonal-contraception 

Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154–1162. doi:10.1001/jamapsychiatry.2016.2387 

https://www.rxlist.com/opill-drug.htm#medguide 

https://go.drugbank.com/drugs/DB09389 

https://www.acog.org/womens-health/faqs/progestin-only-hormonal-birth-control-pill-and-injection#:~:text=Progestin%2DOnly%20Pills%3A%20With%20typical,of%20using%20progestin%2Donly%20pills. 

https://pdf.hres.ca/dpd_pm/00011519.PDF 

https://helloclue.com/articles/cycle-a-z/sex-hormone-binding-globulin-shbg-101#:~:text=Progestin%2Donly%20forms%20of%20birth,SHBG%20(21%2D25) 

Erik Weiner, Arne Victor, Elof D.B. Johansson, Plasma levels of d-norgestrel after oral administration, Contraception, Volume 14, Issue 5, 1976, Pages 563-570, ISSN 0010-7824, https://doi.org/10.1016/0010-7824(76)90007-X. 

National Center for Biotechnology Information. PubChem Compound Summary for CID 13109, Norgestrel. https://pubchem.ncbi.nlm.nih.gov/compound/Norgestrel. Accessed July 25, 2023. 


 

Hormone Metabolism 101 - How the HuMap™ Informs Clinical Practice

Heather Hydzik, ND

 August 2, 2023 at 9:30 AM and 12 PM Pacific

Each session is approximately 60 minutes with Q&A

More and more patients are requesting urinary hormone and metabolite testing, yet many practitioners feel overwhelmed by the depth of information provided in these tests. Join Dr. Heather Hydzik as she guides you through the 4 major hormone pathways (progesterones, androgens, corticoids, and estrogens) and their metabolites to gain proficiency in utilizing the Doctor's Data Hormone and Urinary Metabolites Assessment Profile (HuMap™) to understand individualized hormone metabolism and develop precisely tailored treatment plans.

Learning Objectives:

  1. Review the clinical advantages and limitations of urinary hormone testing contrasted with saliva or serum, and understand how to choose which test to run?
  2. Identify patterns of hormone metabolism revealed by the HuMap™ that relate to hormone health/pathology (i.e. breast cancer, prostate health, PCOS, hair loss, fatigue/insomnia, low libido, erectile dysfunction, mood or cognitive concerns, and more)
  3. Take a tour of the HuMap™ report and discover the clinical highlights of each section
  4. Learn treatment strategies to modulate enzymes and optimize hormone metabolism


 
 

The HuMap™ in Action: Patient Cases

and Treatment Strategies

Heather Hydzik, ND

 Sep 6, 2023 at 9:30 AM and 12 PM Pacific

Each session is approximately 60 minutes with Q&A

Hormone imbalance can impact numerous areas of patient health and well-being including energy, stress, mood, metabolism, weight, sexual health, and more. Urine metabolite testing casts a wide net to analyze steroid hormones and the enzymes that metabolize them in order to guide treatment and improve symptoms.

Join Dr. Heather Hydzik in discussing HuMap™ (Hormone and Urinary Metabolites Assessment Profile) case presentation for both males and females. Cases will include examination of pertinent hormone metabolite imbalances in various hormone pathways: progesterones, corticoids, androgens and estrogens. Precisely tailored treatment plans will be discussed.

Learning Objectives:

  1. Discuss 2 patient cases involving hormone imbalance – 1 female and 1 male
  2. Review interpretation of the HuMap™
  3. Prioritize treatment based on testing and symptoms
  4. Watch testosterone improve without hormone supplementation
  5. Learn how to address issues with estrogen metabolism
  6. See examples of lifestyle and supplemental support to improve HPA axis function
  7. Observe how the HuMap™ report changes along with symptoms after targeted treatment


 
 

Maximize Your Male Hormones

Presented by Pamela W. Smith, M.D., MPH, MS

September 20, 2023 at 12 PM Pacific

Each session is approximately 60 minutes with Q&A

Join internationally known physician, author, and educator, Dr. Pamela W. Smith for this interactive seminar on Maximizing Male Hormones. This discussion will explore the science behind male hormone replacement including aiding sexual function, prevention of heart disease and cognitive decline along with maintaining bone structure and muscle mass. This seminar will examine hormone replacement from A-Z. Have all of your questions answered.

Learning Objectives:

  1. Review the functions of testosterone in the body
  2. Understand the definition of andropause
  3. Explore the signs and symptoms of andropause
  4. Review the medical literature concerning testosterone depletion and increased risk of coronary heart disease
  5. Examine the medical literature regarding testosterone decline and cognition
  6. Review the role estrogen plays in male physiology
  7. Learn new ways to lower estrogen in males
  8. Review the advantages of testosterone replacement related to heart disease and memory
  9. Explore the positive effects of testosterone replacement on blood sugar
  10. Know the contraindications to testosterone replacement


Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.

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