Both effects are reported and both are genuinely contested, and neither has been well studied in women over 40 specifically.

On mood, the largest cohort study found a modest but real increase in the likelihood of starting antidepressants among pill users, though that study only included women up to age 34 and the effect appeared to shrink with age. On libido, the majority of women in the systematic review evidence report either an increase or no change, not a decrease, though a meaningful minority do report lower libido, and there is a real, measurable biological pathway (a hormone-binding protein that rises on the pill and can reduce how much free testosterone is available) even though its direct link to sexual desire is not firmly established.

What to know about this answer

This is a genuinely contested question among credentialed clinicians, particularly on libido, where the mechanistic and clinical-experience camp points to a real biological pathway while the data-focused camp points out that the population evidence mostly runs the other direction.

What the research shows, and which source each finding rests on

A Danish cohort of over 1 million women and adolescents aged 15-34 found combined pill users had a 23% relative increase in first-time antidepressant use compared with non-users, with risk peaking around 6 months of use; the relative risk generally decreased with increasing age within that cohort.

C[1]

In a randomized trial of 340 healthy women aged 18-35, the pill significantly reduced general well-being scores compared with placebo, but effects on depressive symptoms specifically were not statistically significant.

B[2]

A systematic review of 36 studies covering over 13,000 women found that among pill users, 85% reported either an increase or no change in libido and 15% reported a decrease; no significant difference in sexual desire was found for pills containing 20-35 micrograms of estrogen, though libido decreased with the lowest-dose (15 microgram) pills.

A[3]

The pill's estrogen component raises a hormone-binding protein in the blood more than the body's natural estrogen does at an equivalent dose, which lowers the amount of free testosterone in circulation; the causal link from this hormonal change to actual sexual desire is not established.

B[4]

Where the real disagreement is

Each position is shown with its own sources. A position listed here is not necessarily the accepted view.

the pill lowers libido through its effect on free testosterone

sexual-medicine clinicians in the source material

These clinicians describe lowered libido as a known side effect of the pill, driven by the hormone-binding protein rise reducing free testosterone, and describe seeing this pattern clinically alongside other side effects like vaginal dryness.

E[5]

the mechanism is not established and the population data run the other way

a different clinician in the source material

This clinician argues the relationship between the hormone-binding protein and testosterone availability is more complicated than commonly assumed, and that in practice she would try switching the type of estrogen in the pill before assuming testosterone needs to be added.

E[6]

What would settle it: A randomized trial comparing a low-hormone-binding-protein-impact pill (such as the estetrol and drospirenone combination) against a standard estrogen-containing pill, with validated sexual-function measures and paired hormone testing, specifically in women over 40. This trial is designable with existing data but has not been run.

What is really going on here

  1. The largest mood-risk cohort study stopped at age 34 and found the effect shrank with age, so applying its numbers directly to a woman in her mid-40s is an extrapolation the study itself would not fully support.
  2. No study has looked specifically at mood or libido effects of hormonal contraception in women over 40; this remains an open evidence gap on both questions.

Questions for your doctor

  1. Could my current mood or libido changes be related to my contraceptive method?
  2. Would switching to a different pill formulation be worth trying before other changes?
  3. Are there other causes we should rule out before attributing this to the pill?
  4. If we switch, how long should I expect before noticing a difference?

Questions with no answer yet

Do the mood-risk findings from the large Danish cohort, which stopped at age 34 and found the effect shrank with age, actually apply to a woman starting or continuing the pill in her mid-40s?

Not directly studied yet

No research does not mean it does not work, and it does not mean it works. It means nobody has tested it yet.

What is known: The largest mood-risk cohort study included women and adolescents only up to age 34, and found the relative risk generally decreased with increasing age within that cohort; no study has looked specifically at mood effects of hormonal contraception in women over 40.

What would test it: A dedicated cohort or trial measuring mood outcomes in hormonal contraception users specifically in their 40s and beyond.

Does the hormone-binding protein rise on the pill actually cause the libido changes some women report, or is the causal link between that protein rise and sexual desire simply unproven?

Partly studied

What is known: The pill's estrogen component reliably raises a hormone-binding protein that lowers free testosterone, a directly measured effect; but the causal link from this hormonal change to actual sexual desire is not established, and one clinician argues the way testosterone binds this and other binding proteins is more complicated than commonly assumed.

What would test it: A randomized trial comparing a low-hormone-binding-protein-impact pill against a standard estrogen-containing pill, with validated sexual-function measures and paired hormone testing, specifically in women over 40.

Sources

  1. 1.Association of Hormonal Contraception With Depression.Skovlund CW, Morch LS, Kessing LV, Lidegaard O. Association of hormonal contraception with depression. JAMA Psychiatry 2016;73(11):1154-62. · Observational study
  2. 2.A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial.Zethraeus N, Dreber A, Ranehill E, Blomberg L, Labrie F, von Schoultz B, Johannesson M, Linden Hirschberg A. A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial. Fertil Steril 2017;107(5):1238-45. · Randomised trial
  3. 3.The influence of combined oral contraceptives on female sexual desire: a systematic review.Pastor Z, Holla K, Chmel R. The influence of combined oral contraceptives on female sexual desire: a systematic review. Eur J Contracept Reprod Health Care 2013;18(1):27-43. · Systematic review or guideline
  4. 4.Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters.Douxfils J, Klipping C, Duijkers I, et al. Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters. Contraception 2020;102(6):396-402. · Randomised trial
  5. 5.Rachel Rubin, MD. Dr Rachel Rubin: The Truth About HRT and Menopause (video transcript).Review, opinion or mechanism
  6. 6.Jen Gunter, MD. Update from the 2025 Menopause Society Annual Meeting (video transcript).Review, opinion or mechanism

The letter grades the type of study behind a claim, not the answer itself.

This page is general information based on published research and public sources. It is not medical advice and not a personal assessment, and it does not replace a conversation with your doctor. Peritale is a wellness product, not a medical device, and is not intended to diagnose, treat, cure or prevent any disease. For any medical question, speak with a licensed clinician.

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