EndoAxis Clinical Team
Hormonal contraceptives are widely used for birth control and symptom management, but they introduce complex challenges when it comes to interpreting sex hormone panels. For clinicians evaluating patients on hormonal birth control, understanding the pharmacological intent and physiological impact of these medications is critical to determine whether hormone testing is clinically meaningful—or potentially misleading.
Hormonal Contraception and Suppression of the HPO Axis
Most hormonal contraceptives—especially oral contraceptives, the etonogestrel implant (Implanon/Nexplanon), and depot medroxyprogesterone acetate (Depo-Provera)—function primarily by suppressing the hypothalamic-pituitary-ovarian (HPO) axis.
This suppression disrupts the normal pulsatile release of gonadotropin-releasing hormone (GnRH), leading to downstream inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and ultimately ovulation.
The ovaries, which are responsible for endogenous production of estradiol and progesterone, are essentially “turned off.” In this pharmacologic context, measuring serum levels of estradiol, progesterone, or LH/FSH offers little insight into a woman’s true baseline hormone production, as these levels are intentionally reduced or rendered undetectable.
Impact on Androgens and Sex Hormone Binding Globulin
In addition to suppressing ovarian hormone output, synthetic estrogens used in contraceptives—especially ethinyl estradiol—stimulate hepatic production of sex hormone binding globulin (SHBG).
- Elevated SHBG reduces the amount of free, bioavailable testosterone, which may contribute to reduced libido, fatigue, or mood changes in some women.
- Although total testosterone levels may appear within reference range, free testosterone is often significantly diminished, particularly in women on oral contraceptives.
Yet, despite measurable reductions, this finding has limited clinical utility because modifying androgen activity in the context of ongoing SHBG elevation rarely yields symptom relief without adjusting the contraceptive itself.
Why Routine Sex Hormone Testing is Not Recommended on Hormonal Birth Control
Given the intended pharmacological suppression of the HPO axis, testing for endogenous sex hormones while a patient is on systemic hormonal contraception is generally not recommended.
- Test results reflect an artificially altered endocrine environment and cannot be used to make accurate inferences about underlying hormonal imbalances or physiologic function.
- Exogenous synthetic hormones (e.g., ethinyl estradiol, levonorgestrel, medroxyprogesterone) are not detectable on standard sex hormone assays, so the full hormonal landscape cannot be accurately assessed.
Attempting to “correct” hormone patterns while a patient remains on hormonal contraception is also problematic. Adding bioidentical hormones or supplements aimed at modifying estrogen or progesterone levels can disrupt the already medicated hormonal feedback loops, stress hepatic clearance pathways, and worsen symptom burden. Without the ability to adjust endogenous hormone production—which is pharmacologically suppressed—intervention becomes both ineffective and potentially harmful.
The IUD: A Partial Exception
Intrauterine devices (IUDs) such as levonorgestrel-releasing systems (e.g., Mirena, Kyleena) differ from systemic contraceptives in that they exert primarily local effects within the uterus, thickening cervical mucus and thinning the endometrial lining.
- Some systemic absorption does occur, but the degree of HPO axis suppression varies by individual.
- Some women on IUDs continue to ovulate and produce endogenous estrogen and progesterone, while others experience partial or full suppression.
Sex hormone testing in women with IUDs may sometimes yield clinically relevant data—but interpretation must be approached with caution.
Progestins used in IUDs are structurally similar to testosterone and can act as androgen receptor agonists. This androgenic activity may contribute to symptoms like acne, hair thinning, or mood changes, even though overall hormone production remains largely unaffected.
The critical clinical question is: If hormonal dysfunction is detected in a patient with an IUD, what can be done? If the contraceptive is still exerting influence over the hormonal milieu, treatment options are limited. As with systemic contraceptives, any attempt to alter hormone activity without discontinuing or changing the device may result in further dysregulation.
When and How to Support Patients on Hormonal Birth Control
When women on hormonal contraception present with symptoms—such as mood swings, low libido, fatigue, or menstrual irregularities—those symptoms are often a result of the contraceptive itself, not an underlying hormonal imbalance.
Rather than testing sex hormones, a more productive clinical strategy focuses on addressing known nutrient depletions, metabolic disruptions, and systemic effects caused by hormonal contraception:
- Nutrient Testing and Repletion: Oral contraceptives are associated with depletion of magnesium, folate, B12, B6, selenium, and zinc. Repletion may improve energy, mood, and neurologic function.
- GI and Microbiome Assessment: Contraceptives can alter the gut microbiome and impair gut-brain axis function, contributing to mood disorders, immune dysregulation, and gastrointestinal symptoms.
- Thyroid and Adrenal Evaluation: Assessing thyroid function and cortisol patterns may be more useful, particularly in patients with chronic fatigue or metabolic symptoms.
- Liver Support: Of important note, the use of phase I detoxification agents – including diindolylmethane (DIM) or indole-3-carbinol (I3C) – may interfere with the efficacy of hormonal contraceptives (with the exception of IUDs). These compounds accelerate liver clearance of synthetic hormones, which can reduce circulating hormone levels below the threshold required to suppress the hypothalamic-pituitary-ovarian (HPO) axis. As a result, ovulation may occur, increasing the risk of unintended pregnancy.
