Everything you ever wanted to know about birth control
Hormonal contraception.
The informed consent conversation
that was never had.
On SHBG, synthetic progestins, what the HPA axis does when you suppress the HPO axis, and the specific information that was documented in peer-reviewed literature and not incorporated into the prescribing conversation.
I was 17 when I was first prescribed the pill. The appointment lasted perhaps eight minutes. I was told it would regulate my cycle, clear my skin, and prevent pregnancy. I was told to take it at the same time each day. I was given a leaflet listing nausea, headache, and breakthrough bleeding as possible side effects.
I was not told about SHBG. I was not told about synthetic progestins and what receptors they bind beyond the progesterone receptor. I was not told about what happens to the HPA axis when you suppress the HPO axis. I was not told that for some women, certain effects persist long after stopping. I was not told about the olfactory preference reversal, about the cortisol profile changes, about the depression association documented in over a million women.
I was not told any of this — not because my doctor was incompetent or negligent, but because the standard of care for hormonal contraception had quietly decided that women didn't need to know.
This is not an anti-pill post. I want to say that clearly and at the front. The ability to suppress ovulation is one of the most significant pharmacological developments of the twentieth century, and the freedom it has represented for women is real and substantial. This post is not about taking that away.
It is about the specific information that was documented in peer-reviewed literature and not incorporated into the prescribing conversation. That is a different and more precise claim — and it is one the evidence supports.
What hormonal contraception is actually doing
Combined oral contraceptives suppress the hypothalamic-pituitary-ovarian axis — the HPO axis. By providing synthetic estrogen and progestin, they prevent the hypothalamus from releasing GnRH, which prevents the pituitary from releasing FSH and LH, which prevents follicle development and the LH surge that triggers ovulation. This is the mechanism. It is well understood, well documented, and is precisely what contraceptives are designed to do.
What is less discussed is that the HPO axis does not operate in isolation. It is in continuous communication with the hypothalamic-pituitary-adrenal axis — the HPA, or stress response system — with the gut, with the thyroid, and with the liver. Suppressing one axis is not a confined pharmacological action with no other consequences. It has downstream effects on connected systems. Some of those effects are relevant, documented, and absent from the standard consultation.
The first and arguably most significant of those effects is what happens to a protein called sex hormone-binding globulin.
SHBG: the hidden androgen story
The combined oral contraceptive contains synthetic estrogen. One of estrogen's effects on the liver is to stimulate production of sex hormone-binding globulin — SHBG — a binding protein that circulates in the blood and captures sex hormones, rendering them biologically inactive. Bound hormones cannot enter cells. They cannot exert their effects. Free hormones — unbound, circulating — are the biologically active fraction.
SHBG binds both estrogen and testosterone. But its affinity for testosterone is higher. When SHBG levels rise substantially — as they consistently do on combined oral contraceptives, often two to four times above baseline — free testosterone drops dramatically. Panzer and colleagues published a study in 2006 documenting not only that SHBG rose significantly on combined oral contraceptives, but that in a subset of women it remained significantly elevated after stopping the pill — in some cases for years after discontinuation.¹
Free testosterone is not a "male hormone" that women shouldn't need to concern themselves with. In women, it is integral to libido, clitoral sensitivity, energy, mood regulation, motivation, and bone density. A substantial reduction in free testosterone produces effects that are documented and measurable: reduced sexual desire, reduced physical sensitivity, altered mood, flattened energy across the day. These are not hypothetical. They are the pharmacological consequence of dramatically elevated SHBG.
Women presenting with these symptoms — during pill use, or after stopping — were frequently told it was psychological. That their relationship was the issue. That this was simply who they were now. The mechanism that explained their experience was in the literature. It was not in the consultation.
Not all progestins are the same
Here is something that most women who have ever been prescribed hormonal contraception have not been told: the progestin in your contraceptive is not progesterone.
The progestins in hormonal contraceptives are synthetic compounds designed to bind the progesterone receptor with sufficient affinity to suppress ovulation. They do this reliably. What is routinely omitted is that the progesterone receptor is not the only receptor these compounds bind.
Depending on the specific progestin, synthetic progestins also bind androgen receptors, estrogen receptors, glucocorticoid receptors, and mineralocorticoid receptors — with dramatically different affinities and activities depending on the specific molecule.² Levonorgestrel has significant androgenic activity. Drospirenone is anti-androgenic and anti-mineralocorticoid. Cyproterone acetate is so potently anti-androgenic that it is used independently as a treatment for hirsutism and hyperandrogenism in PCOS. Gestodene has meaningful glucocorticoid receptor activity — meaning it interacts directly with the stress axis. Norethindrone has some estrogenic activity and partially converts to ethinylestradiol in the body.
These differences are not trivial footnotes. An androgenic progestin can worsen acne and alter mood through androgen-associated mechanisms. An anti-androgenic progestin affects libido differently and carries different cardiovascular risk profiles. A progestin with glucocorticoid activity interacts with the HPA axis through a direct receptor pathway. Most women have never been told which progestin they are on, let alone what it binds beyond the progesterone receptor. Many are switched between formulations when side effects occur — without being told that the receptor profile has changed, and that this change is pharmacologically significant.
The HPA axis connection
The HPO axis and the HPA axis share limbic and hypothalamic circuitry. GnRH neurons and CRH neurons are anatomically adjacent, functionally connected, and mutually regulatory. Suppressing the HPO axis does not leave the HPA axis untouched.
Women on combined oral contraceptives show measurably altered cortisol profiles compared to naturally cycling women — including blunted cortisol awakening responses and different HPA reactivity to psychosocial stress. The large Danish cohort study published in JAMA Psychiatry in 2016 — following more than one million women across thirteen years — found significantly higher rates of first antidepressant prescriptions and first diagnoses of depression in hormonal contraceptive users compared to non-users.⁴ The association was strongest in adolescent users and in progestin-only pill users. It was not adequately explained by pre-existing conditions, socioeconomic factors, or relationship variables.
The mood effects of hormonal contraception have been dismissed for decades as psychosomatic, as difficult to disentangle from relationship stress, as inconclusive. The dismissal has not been based on the evidence. The Danish study alone enrolled over a million participants with thirteen years of follow-up. Its methodology was robust. Its findings were not marginal. They were not incorporated into prescribing guidelines.
A randomised controlled trial published in the Journal of Sexual Medicine in 2017 — one of the first of its kind for combined oral contraceptives and sexual function — found that women on combined oral contraceptives showed significantly lower scores for desire, arousal, and satisfaction compared to women on placebo.³ The study was double-blind. The results were significant. They have not changed the standard consultation.
The mechanism this post leads to
There is one further effect that I am going to name here and address fully in the next post, because it belongs in both conversations.
Combined oral contraceptives change the olfactory-immune preference system that operates continuously in naturally cycling women. Women on the pill show a documented reversal of MHC-based odour preferences: they prefer the smell of immunologically similar individuals rather than dissimilar ones — the opposite of what the unmediciated cycle produces. The significance of this, the biology behind it, and what it means for long-term partner compatibility are the subject of what follows.⁵
For the purpose of this post, the single relevant point is: this mechanism is published, it is documented, and it was not in the consultation.
What was documented and when
The specific claim of this post is narrow and precise: these mechanisms were published in peer-reviewed literature, they were not systematically incorporated into prescribing conversations, and women were not given the information to make genuinely informed decisions. These are separable claims, and each one is supported by the evidence.
SHBG elevation and its possible persistence post-discontinuation: published in the Journal of Sexual Medicine, 2006, Panzer et al. The paper has been cited over 400 times. It did not change the consultation.
Progestin receptor binding profiles and their clinical differentiation: this pharmacological information is the basis of formulation differences that pharmaceutical companies are fully aware of. It is not passed to patients.
The depression and antidepressant association: published in JAMA Psychiatry, 2016, Skovlund et al., over one million participants, thirteen years of follow-up. It did not change the consultation.
The MHC olfactory reversal: published in the Proceedings of the Royal Society, 2008. Documented in the scientific literature for nearly two decades. Not in the consultation.
The appropriate response to this record is not to stop your contraceptive tomorrow. It is to be precise about what was withheld, and from whom, and for how long. And to start asking different questions of the systems that are supposed to be working in your interest.
What to do with this
- Know which progestin you are on by name. Not just the brand. The actual synthetic progestin. If your doctor or pharmacist can't tell you without looking it up, look it up yourself. Levonorgestrel, drospirenone, norethindrone, gestodene, desogestrel, cyproterone acetate — these are not interchangeable. They have different receptor profiles and different clinical effects.
- If sexual function or energy has changed significantly, ask specifically about SHBG and free androgen index. SHBG and free androgen index (FAI) can be measured from a blood test. They are not part of routine hormonal panels, but they are clinically available. If sexual desire, clitoral sensitivity, or energy have changed markedly since starting hormonal contraception, these values give you something concrete to work with — rather than being told it's psychological.
- If stopping hormonal contraception, plan for a longer transition than you expect. The HPO axis typically takes three to six months to re-establish reliable cyclicity after combined oral contraceptive use. SHBG may take six to twelve months or longer to normalise. The hormonal state you experience in the first one to three months post-pill is not necessarily your baseline. Track your cycle data — BBT, cycle length, luteal phase — before concluding what your natural rhythm is.
- Treat a formulation switch as a pharmacological change, not a minor adjustment. Changing from a levonorgestrel-based pill to a drospirenone-based pill is not the same as changing pill brands. The receptor profile has changed. What the progestin is binding beyond the progesterone receptor has changed. Effects on mood, libido, skin, water retention, and cardiovascular risk all differ between formulations. Monitor accordingly, and don't attribute changes in wellbeing to other causes if the timing corresponds to a prescription change.
- Document your symptom timeline. If you start or stop hormonal contraception and notice changes — in mood, libido, energy, cycle pattern, skin, cognition — record the timing. The temporal relationship between a pharmacological change and a symptom change is clinical data. It belongs in the conversation with your healthcare provider, and having a documented timeline rather than a vague recollection makes that conversation considerably more productive.
The prescription was not incomplete by accident. The consultation was not eight minutes by chance. The question of what women are entitled to know about medications that alter their hormonal architecture — for months, for years, sometimes for decades — has been answered consistently and repeatedly in favour of simplicity over information.
The information exists. It has existed for a long time. The post you've just read draws entirely on published, peer-reviewed research. None of it is controversial within the scientific literature. All of it should have been in your consultation.
The gap between what is known and what is told is not a scientific failure. It is a political one. And naming it precisely — rather than simply accepting that medicine is complex and doctors are busy — is the beginning of asking for something different.
– Nina- Panzer, C., Wise, S., Fantini, G., Kang, D., Munarriz, R., Guay, A., & Goldstein, I. (2006). Impact of oral contraceptives on sex hormone-binding globulin and androgen levels: a retrospective study in women with sexual dysfunction. Journal of Sexual Medicine, 3(1), 104–113. doi:10.1111/j.1743-6109.2005.00198.x
- Sitruk-Ware, R. (2004). Pharmacological profile of progestins. Maturitas, 47(4), 277–283. doi:10.1016/j.maturitas.2004.01.001
- Zethraeus, N., Dreber, A., Ranehill, E., Blomberg, L., Labrie, F., von Schoultz, B., Johannesson, M., & Hirschberg, A.L. (2017). A first-ever randomized trial of combined oral contraceptive and sexual function. Journal of Sexual Medicine, 14(1), 85–97. doi:10.1016/j.jsxm.2016.11.006
- Skovlund, C.W., Mørch, L.S., Kessing, L.V., & Lidegaard, Ø. (2016). Association of hormonal contraception with depression. JAMA Psychiatry, 73(11), 1154–1162. doi:10.1001/jamapsychiatry.2016.2387
- Roberts, S.C., Gosling, L.M., Carter, V., & Petrie, M. (2008). MHC-correlated odour preferences in humans and the use of oral contraceptives. Proceedings of the Royal Society B, 275(1649), 2715–2722. doi:10.1098/rspb.2008.0825