Cycle mapping - how best to monitor your menstrual cycle

Cycle mapping is the process of monitoring the female hormone profile throughout the menstrual cycle, essentially to detect if ovulation has occurred. It requires testing on multiple days throughout the cycle to detect changes in these hormones. It is important to mention that this can only be done if you aren’t take any hormones in any form, whether that be for contraception, menopause, or menstrual control.

The female menstrual cycle results in changes in 2 pituitary hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and 2 ovarian hormones, oestrogen and progesterone. Ovulation has to occur for these hormones to change in their predicted ways.

The current recommendations for monitoring the menstrual cycle rely on testing progesterone levels in the blood serum 7 days prior to the start date of the next menstrual period. No other tests for monitoring the menstrual cycle are currently recommended by the national guidelines. There are many challenges with relying on this one test. The correct timing of the test can only be proven retrospectively, which can result in the test being taken at the incorrect time in the cycle. Progesterone levels also fluctuate hour to hour on the same day, particularly during the mid to late luteal phase (the exact time they are taken to detect ovulation), and therefore may give a false low reading when an hour later it would have been high enough to show a positive test.

There are multiple tests available privately, some of which might have a role.

The ‘gold standard’ for assessing ovulation is serial transvaginal ultrasound monitoring of follicular development and ovulation. This however is invasive, time consuming and costly and therefore is not done outside of fertility treatment.

Oestrogen tests measure one of three components: estrone (E1), estradiol (E2), or estriol (E3) in the blood or urine. Levels fluctuate hourly, in addition to the cyclical trend, so a single blood test only detects the estradiol level at that second in time. Testing from urine will show what the estradiol level has been on average since the last time urine was passed. It is therefore likely to be more accurate from urine testing, especially if tested first thing in the morning, than a single blood sample.

  • E1 is directly converted from androstenedione (from the adrenal gland) or indirectly from other androgens. This can also be produced by the ovaries and placenta, testicles, and adipose (fat) tissues. E2 and E1 can be converted into each other as needed. E1 is the primary estrogen in men and post-menopausal women.

  • E2 is primarily produced in the ovaries under stimulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pre-menopausal women and men’s testicles. Converted from E1 in post-menopausal women, E2 is the most potent estrogen, the one present in the highest concentration in non-pregnant, pre-menopausal women. E2 levels vary depending on a woman’s age and reproductive status. They are a good marker of ovarian function.

  • E3 is produced by the placenta, with concentrations rising throughout a woman’s pregnancy. Very low levels of E3 are present in non-pregnant women or men.

Progesterone can be detected in a blood sample but it is only excreted in the urine as its metabolite, the main one being pregnanediol. Urine testing therefore relies on a surrogate marker, the levels of the metabolite. Like oestrogen, it fluctuates hourly within the cyclical trend so urine testing gives you more information about the average level than a single serum sample.

There is a widely held belief that if you are having regular periods you are ovulating, the thinking being that 92-97% of regular cycles are ovulatory, but a large population study showed that possibly up to a third of women are not ovulating based on detecting a blood test rise of progesterone. Does this mean that this method of testing is inaccurate almost a third of the time, or previous estimates of ovulation are inaccurate?

In addition to issues around irregular cycles, some women have a short luteal phase, ie there is less than 10 days from ovulation to the start of menses, and this might be incorrectly diagnosed as not having ovulated if purely relying on a single progesterone level 7 days prior to the period starting.

The most common test available is urine testing of LH to detect ovulation which is marketed to assist with fertility. It has been shown that urine testing of LH is comparable to serum blood testing and therefore can be relied upon. As semen can last for up to 7 days in the female reproductive organs, timing sexual intercourse exactly to ovulation is not recommended as it could result in missed opportunities prior to the LH surge. Clearblue sell these in packs of 10 test strips and cost £27.99 and just give you a yes or no answer.

Testing for oestrogen has been added to some of these testing kits to pick up the fertile window prior to ovulation so that the lifespan of a sperm can be optimised. This means that women with an irregular menstrual cycle, or with a short luteal phase can adequately detect their fertile window, and to time sexual intercourse if that is required for personal reasons. However, just because you had a LH surge doesn’t necessarily mean that your ovaries responded appropriately and an egg was released. Clearblue sell these in packs of 10 test strips and cost £28.99 and give you a yes or no answer. Mira will track the actual values and chart these for you; the monitor costs £209 with enough strips to track one cycle and replacement wands for future cycle tracking are £69.

Mira and Proov can also subsequently detect the progesterone surge with ovulation to confirm that ovulation did in fact occur. Proov give a yes or no answer and costs £36, Mira provides numerical values and costs £240 and £90 for each additional cycle.

References

[1] Roos J, Johnson S, Weddell S, Godehardt E, Schiffner J, Freundl G, Gnoth C. Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation. Eur J Contracept Reprod Health Care. 2015;20(6):438-50. doi: 10.3109/13625187.2015.1048331. Epub 2015 May 27. PMID: 26018113.

[2] Edelman A, Stouffer R, Zava DT, Jensen JT. A comparison of blood spot vs. plasma analysis of gonadotropin and ovarian steroid hormone levels in reproductive-age women. Fertil Steril. 2007 Nov;88(5):1404-7. doi: 10.1016/j.fertnstert.2006.12.016. Epub 2007 Mar 26. PMID: 17368453; PMCID: PMC2175208.

[3] Newman M, Curran DA. Reliability of a dried urine test for comprehensive assessment of urine hormones and metabolites. BMC Chem. 2021 Mar 15;15(1):18. doi: 10.1186/s13065-021-00744-3. PMID: 33722278; PMCID: PMC7962249.

[4] Newman M, Pratt SM, Curran DA, Stanczyk FZ. Evaluating urinary estrogen and progesterone metabolites using dried filter paper samples and gas chromatography with tandem mass spectrometry (GC-MS/MS). BMC Chem. 2019 Feb 4;13(1):20. doi: 10.1186/s13065-019-0539-1. PMID: 31384769; PMCID: PMC6661742.

[5] Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin Invest. 1984 Jun;73(6):1638-47. doi: 10.1172/JCI111370. PMID: 6427277; PMCID: PMC437074.

[6] Handelsman DJ, Nimmagadda R, Desai R, Handelsman TD, Whittle B, Skorupskaite K, Anderson RA. Direct measurement of pregnanediol 3-glucuronide (PDG) in dried urine spots by liquid chromatography-mass spectrometry to detect ovulation. J Steroid Biochem Mol Biol. 2021 Jul;211:105900. doi: 10.1016/j.jsbmb.2021.105900. Epub 2021 Apr 17. PMID: 33872762.

[7] Prior JC, Naess M, Langhammer A, Forsmo S. Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A Population-Based Cohort from HUNT3, Norway. PLoS One. 2015 Aug 20;10(8):e0134473. doi: 10.1371/journal.pone.0134473. PMID: 26291617; PMCID: PMC4546331.

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