IVF Reads / Hormones in Female Reproduction: What Goes Wrong
Hormones in Female Reproduction: What Goes Wrong
Irregular or absent periods usually mean ovulation is not happening reliably rather than that one hormone is low. Thyroid function, prolactin, androgens, gonadotropins and a pelvic ultrasound separate the common causes, and the 2023 international PCOS guideline recommends letrozole as first-line treatment for ovulation induction in anovulatory PCOS (recommendation 5.3.1).
- The cycle is driven by pulsatile GnRH from the hypothalamus, which drives pituitary FSH and LH; ovarian estradiol and progesterone feed back on both. Continuous rather than pulsatile GnRH suppresses FSH and LH, which is the mechanism GnRH agonist drugs use (StatPearls, Physiology, Follicle Stimulating Hormone, NBK535442).
- The 2023 International Evidence-based Guideline for PCOS (Hum Reprod 38:1655-1679), recommendation 5.3.1: letrozole should be the first-line pharmacological treatment for ovulation induction in infertile anovulatory women with PCOS and no other infertility factors. Recommendation 5.4.5.1 states letrozole should be used rather than clomiphene citrate.
- The same guideline notes at 5.3.2 that letrozole remains off-label for this use in many countries, and that where it is not permitted clinicians could use other ovulation induction agents.
- The 2023 PCOS diagnostic criteria are hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology on ultrasound or, new in 2023, AMH in place of ultrasound. Recommendation 1.5.3 states serum AMH should not be used as a single test for diagnosis.
- ASRM's 2021 committee opinion on luteal phase deficiency (Fertil Steril 115:1416-1423) states that luteal phase deficiency has not been proven to be an independent entity causing infertility or recurrent pregnancy loss.
Which hormone problem causes irregular or absent periods?
In most cases it is not one hormone being low — it is that ovulation is not happening reliably, and several different upstream problems produce that same result. Four causes account for most of what is found: polycystic ovary syndrome, thyroid disease, a raised prolactin, and low hypothalamic drive from very low body weight, heavy training or illness.
They are separated by a short set of tests rather than by symptoms, because the symptoms overlap. What matters for you is that these four have different treatments, so the test result changes what happens next.
A missed or late period is also, commonly, an early pregnancy. That is ruled out first, before any of this.
How does the brain-ovary axis actually run a cycle?
Three levels, in order. The hypothalamus releases GnRH in pulses. Those pulses make the pituitary release FSH and LH. FSH recruits a cohort of ovarian follicles, which grow and make estradiol.
Estradiol initially feeds back negatively and damps FSH down, which is how one dominant follicle wins and the rest regress. Then, at a high enough level and for long enough, that feedback flips positive and triggers the LH surge. Ovulation follows the start of the surge by roughly a day and a half. The emptied follicle becomes the corpus luteum and makes progesterone, which holds the lining steady; if there is no pregnancy it fades, progesterone falls, and the lining sheds.
Two practical consequences fall out of that. First, the pulses matter as much as the amounts: continuous rather than pulsatile GnRH suppresses FSH and LH instead of driving them, which is exactly how GnRH agonist drugs shut the axis down in IVF. Second, progesterone only appears after ovulation, which is why a mid-luteal progesterone is used to confirm ovulation happened at all.
If you want this one level deeper on the estrogen side, that is covered separately in what estrogen does across one cycle.
Which tests separate the common causes?
A typical first round is short. What each is for:
- TSH and free T4 — thyroid disease disturbs cycles in both directions and is cheap to exclude.
- Prolactin — a raised prolactin suppresses GnRH, which lowers FSH and LH and stops ovulation. It has its own treatment, so finding it changes the plan.
- Total testosterone, sometimes with SHBG — for the hyperandrogenism limb of the PCOS criteria.
- FSH, LH and estradiol on day 2 or 3 — mainly to tell an ovarian problem (FSH high) from a pituitary or hypothalamic one (FSH and LH both low).
- Pelvic ultrasound — antral follicle count and ovarian morphology. In 2023 AMH became an accepted alternative to ultrasound in adults for defining polycystic ovarian morphology.
- Mid-luteal progesterone — confirms that ovulation occurred in that cycle.
The 2023 PCOS guideline is worth knowing on one point here: where irregular cycles and hyperandrogenism are both present, diagnosis is simplified and neither ultrasound nor AMH is required. It also recommends not doing both AMH and ultrasound, specifically to limit overdiagnosis. If you are being sent for both, that is a fair question to ask.
What gets treated first when ovulation is the problem?
It depends on the cause, and that is the argument for testing before treating.
- PCOS with anovulation and no other infertility factor: the 2023 guideline recommends letrozole as the first-line drug, and recommends it ahead of clomiphene citrate. Note the guideline's own caveat at 5.3.2 — letrozole is still off-label for this indication in many countries, and where it is not permitted other ovulation induction agents are used.
- Thyroid disease: the thyroid is treated, and cycles commonly settle without any fertility drug.
- Raised prolactin: the cause of the raised prolactin is addressed. Ovulation induction is not the starting point.
- Low hypothalamic drive: restoring energy availability and weight is the treatment. Drugs that push the pituitary do not fix an axis that has been switched off deliberately.
None of the above is IVF, and for anovulation alone it usually should not be. Ovulation induction with timed intercourse is the cheaper and simpler route, and the guideline treats IVF as a later step rather than a first one.
What the evidence does not establish
Where the honest answer is that the evidence is thinner than the marketing:
- It does not establish that a single hormone is 'imbalanced' and needs correcting. There is no test that reports an imbalance; there are tests that identify specific named conditions.
- It does not establish luteal phase deficiency as a cause of infertility. ASRM's 2021 committee opinion states that it has not been proven to be an independent entity causing infertility or recurrent pregnancy loss.
- It does not establish that ovarian reserve tests predict whether you will conceive. ASRM's 2020 committee opinion states these markers are poor predictors of reproductive potential independently from age, and Steiner's cohort of 750 women aged 30-44 found a raised FSH was not associated with reduced fertility.
- It does not establish that a supplement, detox or diet protocol restores ovulation. Where energy availability or weight is the cause, changing that is treatment; a branded product is not the same claim.
- It does not establish that a normal set of hormones means nothing is wrong. Tubes, the uterus and semen quality are not measured by any of these tests.
Being handed a list of hormone names with no sense of which one matters is genuinely disorienting, and that is a problem with how results are reported rather than a sign that your case is complicated.
Not sure what your results mean?
Upload your test results and IVY will explain what has been checked, what it shows, and what usually comes next.
My doctor has already started me on medication — should I stop?
No. Nothing here is a reason to stop something a doctor has prescribed, and stopping an ovulation induction drug or a thyroid medicine part-way through is its own risk. Your doctor has your history, your ultrasound and your examination, none of which an article has.
What this page is useful for is asking better questions at the next appointment: which cause was found, which test showed it, what this drug is meant to change, how long before we know whether it worked, and what happens if it does not.
Related reading
Keep reading
6 Sources
- Teede HJ, Tay CT, Laven J, et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Hum Reprod 2023;38:1655-1679. Recommendation 5.3.1: letrozole should be the first-line pharmacological treatment for ovulation induction in infertile anovulatory women with PCOS with no other infertility factors. 5.4.5.1: letrozole should be used rather than clomiphene citrate. 5.3.2: letrozole is still off-label in many countries. 1.5.3: serum AMH should not be used as a single test for diagnosis. ESHRE / ASRM / Monash University
- Practice Committees of the American Society for Reproductive Medicine and the Society for Reproductive Endocrinology and Infertility. Diagnosis and treatment of luteal phase deficiency: a committee opinion. Fertil Steril 2021;115:1416-1423. States that although progesterone is important for implantation and early embryonic development, luteal phase deficiency has not been proven to be an independent entity causing infertility or recurrent pregnancy loss. This document replaces 'Current clinical irrelevance of luteal phase deficiency', last published in 2015. American Society for Reproductive Medicine
- Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril 2020;114:1151-1157. Markers of ovarian reserve are useful predictors of oocyte yield after controlled ovarian stimulation but are poor predictors of reproductive potential independently from age. American Society for Reproductive Medicine
- Steiner AZ, Pritchard D, Stanczyk FZ, et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA 2017;318:1367-1376. Prospective time-to-pregnancy cohort of 750 women aged 30-44 with no infertility history: biomarkers indicating diminished ovarian reserve were not associated with reduced fertility. JAMA
- Physiology, Menstrual Cycle. StatPearls. NCBI Bookshelf NBK500020. Background physiology of the hypothalamic-pituitary-ovarian axis: the switch from negative to positive estradiol feedback, the LH surge, and ovulation following the onset of the surge. StatPearls / NCBI Bookshelf
- Physiology, Follicle Stimulating Hormone. StatPearls. NCBI Bookshelf NBK535442. FSH is released by the anterior pituitary in response to hypothalamic GnRH and acts on ovarian granulosa cells. Continuous rather than pulsatile GnRH suppresses FSH and LH release, which is the mechanism behind GnRH agonist drugs. StatPearls / NCBI Bookshelf
Frequently asked questions
Common questions on this topic.
How many days of cycle variation is worth investigating?
Cycles that consistently run shorter than about 21 days or longer than about 35, or that swing widely month to month, are the ones usually looked into, because that pattern suggests ovulation is not happening on a regular schedule. A single odd month after illness, travel or a stressful stretch is common and not by itself a reason for tests.
Can stress alone stop my periods?
Low hypothalamic drive is a real and recognised cause of absent periods, and it is triggered by the body sensing insufficient energy — which severe psychological stress, heavy training and under-eating can all contribute to. It is a diagnosis made by excluding the other causes first, not one assumed because a stressful period coincided.
Is PCOD the same thing as PCOS?
In Indian clinical usage the two terms are often used interchangeably for the same condition. The 2023 international guideline uses PCOS throughout and defines it by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology, so that is the framework worth asking about regardless of which label appears on your report.
Will ovulation induction give me twins?
Multiple pregnancy is a recognised risk of ovulation induction rather than a certainty, which is why cycles are monitored by ultrasound rather than run blind. The size of the risk differs by drug and by protocol, so it is a question for the doctor prescribing yours; this page does not carry a figure for it.
Do I need my hormones tested again after treatment starts?
Monitoring during an ovulation induction cycle is usually done by ultrasound to watch follicle growth, with a progesterone level afterwards to confirm ovulation happened. Repeating the full diagnostic panel is not routine once the cause has been identified.
Can hormone problems affect my partner too?
Male hormone problems exist and are investigated differently, starting from a semen analysis rather than a hormone panel. The relevant point for a couple is that a female hormone diagnosis does not rule out a male factor, and both are usually assessed at the same time rather than one after the other.

