Why "21 day progesterone" testing is a poorly named practice

Day 21 progesterone 

 We hear this term a lot right? Day 21 progesterone test

First I want to explain what progesterone is and why your doctor may be looking at it. Then I will explain why it's a poorly named test and when you might want to think about having your blood drawn to test your levels on a day that is completely unique to you. 

Progesterone is a steroid hormone in the body that has long been recognized as a vital hormone for pregnancy. It helps to prepare the body to implant a fertilized egg, as well as maintain pregnancy by its effect on the uterine lining. Progesterone rises around seven days post ovulation and will continue to hold if implantation has occurred. 

Here I am going to get into the nerdy of it and read from this article on the National Institute of health which I will drop below. 

 In this episode I will break down an article by the NIH that is a deep dive into the role of hormones, especially Progesterone on the female body during the pre ovulatory, ovulatory and post ovulatory stages. 

 Okay so I know not everyone wants to read lengthy articles so I am here to do it for you in a less dry manner. If you want to skip this video though I suggest watching to the end. Check out my 21 day progesterone video and my Egg quality video that also explain some of the steps you can take to look into your hormone function and how to support your egg quality with nutrients. 

And as a disclaimer I am a licensed massage therapist, Doula and Personal trainer but I am not a Doctor and nothing I say should be taken as medical advise I am just a woman who has struggled with infertility and is sharing some of the things I used to calm my nerves during the process and educate myself so I could feel empowered through my own Journey and I hope you feel the same! 

“In fertile women, sex steroids are synthesized cyclically, and their action determines the menstrual cycle. Steroid synthesis starts in the follicles, which are the functional units of ovaries. Each follicle consists of a single oocyte surrounded by somatic granulosa cells”. 

Oocyte being the little egg before it is fertilized

“These are called primordial follicles, and each woman has a finite supply of these follicles starting at birth?, 

Which is an amazing fact that in our mothers womb we have all of the eggs we will ever have and since our mothers also started with all of their eggs the oocyte that became us technically started in our 

  Within the first menstrual cycle, a selected amount of primordial follicles start to develop and form so-called pre-antral follicles. During early development, the follicles recruit theca cells, which become vascularized and secure the transport of hormones. Under the stimulation of luteinizing hormone (LH), these theca cells start to synthesize androgens, which are converted to estrogens in somatic granulosa cells via stimulation of follicle-stimulating hormone (FSH) and the aromatase system.

If you have ever looked into estrogen dominance or PCOS these terms might be familiar to you. Excess androgens can turn into increased estrogen or estrogen dominance which can lead to masculine traits in women, weight gain, facial hair and a host of other imbalances. It can also throw off the balance of Progesterone and be a culprit in infertility especially among women today thanks to the amount of Xenoestrogens in our environment. 

 The theca cells also synthesize PROG, which acts directly on granulosa cells and promotes follicular growth. When a growing follicle reaches 200–300 μm in diameter, a fluid-filled cavity containing follicular fluid starts to form; these are called antral (secondary) follicles. As the follicle matures, the concentration of estradiol and PROG reaches levels 1–10,000-fold higher than in circulation. In addition, Antimüllerian hormone, inhibin-A and inhibin-B are also synthesized by the granulosa cells. Inhibin-B has been suggested to attenuate pituitary FSH secretion and may augment theca cell androgen production in synergy with LH. These mechanisms are likely to play important functions in the process of selecting the dominant follicle (Graaf follicle) [49]. 

Dominant follicles are the candidates if you will for ovulation. In monitored cycles they will look at the ovaries and measure which follicle or follicles they believe to be dominant, thus determining which ovary you will ovulate from and in fertility treatments which follicle will be harvested for egg retrieval. 

The dominant follicle also synthesizes PROG and may reach up to 2 cm in diameter. These processes occur in the follicular phase of the menstrual cycle (up to days 12–14). 34–36 hours after the LH surge, ovulation occurs, with the dominant follicle passing into the Fallopian tube where it can be fertilized. The dominant follicle becomes the corpus luteum, which synthesizes PROG in the luteal phase (after ovulation to the end of the cycle) [50].

This progesterone relationship can identify problems with the luteal phase such as luteal phase defect where progesterone is low and may allow for shorter cycles or spotting in between cycles. There can also be uncomfortable symptoms like PMS thanks to lack of this hormone but it is not the only cause of these. 

 In the corpus luteum, PROG is synthesized in two enzymatic steps. The first is the conversion of cholesterol to pregnenolone in the mitochondria (cholesterol side chain cleavage enzyme P450scc), and the second is the conversion of pregnenolone to PROG (3β-hydroxysteroid dehydrogenase) [2]. The PROG serum concentration in the follicular phase is lower than 1 ng/mL, but after ovulation, its levels reach 10–35 ng/mL. Stress during the follicular phase may slightly elevate PROG levels (up to 1.6 ng/mL). The corpus luteum secretes PROG continually in the early luteal phase, while in the mid-and late-luteal phase, the PROG secretion reflects the LH pulsatile release. The PROG peak is reached in the mid-luteal phase. In the absence of conception, the corpus luteum decays 9–11 days after ovulation [2,10]. PROG plays a key role in endometrial proliferation. The expression of PROG, as well as estradiol receptors, varies during the menstrual cycle. In the follicular phase of the menstrual cycle, the estrogen receptors predominate, decreasing during ovulation due to the suppressive effects of PROG. In the ovulatory phase, PRs increase exponentially and decrease in the late-ovulatory phase.

In the case of conception, the embryo enters the uterus about 2–3 days after fertilization, and implantation begins 5–6 days later. PROG levels do not increase during this period. Later, the corpus luteum produces PROG until the 8th–9th week of pregnancy. Thereafter, PROG starts to be synthesized by trophoblasts, and after the 12th week of gestation, the placenta is the largest source of PROG. In early pregnancy, levels vary between 10–40 ng/mL and rise to 100–200 ng/mL in late pregnancy [51]. PROG is mainly synthesized from maternal LDL cholesterol by the placenta, with only a minor proportion formed by fetal steroidogenesis. PROG promotes endometrial maturation and uterine vascularization in the pre-implantation phase.

PROG is metabolized primarily in the liver by 5α-reductase and 3β-hydroxysteroid dehydrogenase, resulting in a number of metabolites discussed later. However, the enzymes necessary for PROG metabolism are present in other tissues, especially the corpus luteum, adipose tissue, vaginal mucosa, skin and also in the brain”.

Okay so now that we know more than we ever wanted to about progesterone let me tell you why the name is so silly. 

 And it's simple. We don’t all ovulate on the same day and we certainly don’t all have the same cycle lengths do we? No so while I personally ovulate between days 14 and 15 of my cycle and my luteal phase lasts 14 days so 7 DPO often does fall on day 21 of my cycle, it doesn’t always and many women have shorter or longer cycles. So your day 21 may only be five days past ovulation or more or even less. So it is important to track your cycles however you find most comfortable. f=For me, it is the Inito app or the Mira Wand that test hormone metabolites through the cycle and let me know when my progesterone is rising to prove that I have ovulated. Once you know when your ovulation day was in that cycle you will want to wait 7 days to then go for bloods if you are trying to determine your levels. 

   The reason for this can vary. Some women have more or less progesterone on these days and are perfectly healthy and some like me trend low which has led to me supplementing with progesterone vaginally in suppository form to help implantation stick. After multiple losses and an ectopic tubal removal. I take bioidentical progesterone after suspected implantation within the luteal phase and sometimes earlier depending on my doctor's recommendations that month. 

   Fertility can be a lot, but knowing the when and why can make sense of a daunting time and give some method to the madness. 

     I hope you enjoyed this episode of Rainmaker Somatics: The open womb women’s wellness podcast 

Kolatorova L, Vitku J, Suchopar J, Hill M, Parizek A. Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int J Mol Sci. 2022 Jul 20;23(14):7989. doi: 10.3390/ijms23147989. PMID: 35887338; PMCID: PMC9322133.