Introduction

All women experience changes to their bodies as they age.

You probably remember the first big biological change, marked by the arrival of your first period. For some, this was a celebratory day marking your entrance into ‘womanhood’. Equally likely, this may have been an experience filled with shame, fear, anxiety or embarrassment. You may have been provided with information openly, you may have been handed a Judy Blume novel about the trials of puberty, or you may have gotten no information at all, leaving you completely in the dark about what was happening.

Regardless of whether or not you received any information or support, one thing was assured – you had to figure out how to take care of your body and how to continue your daily life while dealing with very tangible, monthly evidence that you had now officially reached reproductive age.

We are all growing older every day, but many women don’t realize that medically, there is a reproductive clock that ticks alongside, but not always in sync with, their biological clock (despite the common use of ‘the biological clock’ indicating how much time a woman has left to bear children). It is this reproductive aging process that determines when you enter into the transition to menopause and finally pass menopause and settle into post-menopausal life.

The Reproductive Clock

Learn More

Understanding the reproductive clock

Menopause can be such a mystery that it is no surprise we don’t even have common language to describe the entire experience. Many of us describe the experience of our changing bodies as ‘starting menopause’. We are equally likely to say we have entered perimenopause. For the purposes of accuracy, note that menopause is a singular event that is marked when you don’t get a period for a full year. Before that, you are in the menopausal transition and after that you are postmenopause. Scientifically, perimenopause covers the entire menopausal transition and the early part of post-menopause. Herstasis uses this consistent terminology shown in Figure 1 below – reproductive age, menopausal transition and postmenopause. Figure 1 shows your reproductive clock – the three stages of your reproductive age overlaid with your hormonal activity.

There is only one easy-to-identify external sign that you’ve formally entered into reproductive aging – the arrival of your first period, technically termed “menarche”. After that, signs that you are moving into a different stage are extremely subtle and usually need to be confirmed with lab tests.

Unfortunately for women, information about entering into the most tumultuous stage – the menopause transition – is hard to come by. There are physical signs, usually in the form of unpleasant symptoms, that you have entered into the ‘wild ride to menopause’, but no one marker is as easily identified as menarche. If you have studiously tracked your periods and know your cycles well, it may be easier to pick up movement through the stages, but still not guaranteed.

So remember, discussion of menopause and the menopausal transition needs to be linked to your reproductive age, not your biological age. The average biological age for women to experience menopause is 51, but it can come at an earlier or later biological age, even before 40 (although this is rare and is called premature menopause).

Download PDF

Figure 1: The female reproductive clock – the three stages of your reproductive age and corresponding hormone levels. [1]

One of our key goals at Herstasis is to bring easy, home based, accurate technology to individual women so they can gather as much information as possible about their own reproductive aging process in order to (i) be informed (it is your body after all!) and (ii) to advocate for your own care.

The Menstrual Cycle

Learn More

Download PDF

Figure 3: An Outline of the key elements in a Menstrual Cycle

The menstrual cycle involves the monthly release of an egg from one of the ovaries, called ovulation. The uterus prepares to receive a fertilized egg via a series of hormonal changes. If the egg does not get fertilized by a sperm cell then the lining of the uterus isn’t needed and it is shed through the vagina – resulting in a menstrual period. [4]

This menstrual cycle is driven by changes in hormones, particularly estrogen, progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (pituitary hormones). Estrogen and progesterone are called ‘sex hormones’ because they are secreted by your ovaries, which are the female sex organs. LH and FSH are gonadotropins because they are secreted from cells in the anterior pituitary called gonadotrophs (gonads are the formal term for the sex organs – ovaries in females, and testes in males).

There are three stages in the menstrual cycle: the follicular stage (before release of the egg); the ovulatory stage (egg release); and the luteal stage (after egg release). 

The first day of menstrual bleeding marks the first day of the follicular phase. At this time, levels of estrogen and progesterone are low and the top layers of the thickened lining of the uterus (endometrium) break down and shed, creating the menstrual bleeding. At the same time, follicle-stimulating hormone (FSH) levels increase and cause several follicles, each containing an egg, to develop in the ovaries. Then the FSH levels start to decrease and only one follicle continues to develop and starts to produce estrogen. 

This becomes the ovulatory phase when luteinizing hormone (LH) and FSH both rapidly increase. LH causes the egg to be released from the follicle (ovulation). Estrogen levels decrease when LH and FSH levels are heightened. Progesterone levels begin to increase. 

In the luteal phase both LH and FSH levels decrease. A structure called the corpus luteum forms from the ruptured follicle (that just released the egg) and it begins to produce progesterone. Estrogen levels stay elevated for much of the luteal phase. The presence of progesterone and estrogen cause the uterine lining to thicken in preparation for the implantation of a fertilized egg.

If the egg isn’t fertilized, the corpus luteum breaks down and stops producing progesterone. Estrogen levels also decrease. This causes the top layers of the uterine lining to break down and begin shedding, starting menstrual bleeding and the beginning of a new menstrual cycle. [4] [5]

Download PDF

What does this mean for me?

Learn More

What does this all mean for me?

Knowledge is power, and personal knowledge is even more powerful. Most women are frustrated during the menopause transition because they can’t get clear answers about what is happening in their own bodies. Some may be experiencing debilitating symptoms. Others may want to understand possible therapies and the implications of those therapies. Many women just need to be heard and reassured that what they are experiencing is normal, that they aren’t “crazy” or “dying”. They want to understand what symptoms are transient versus what ones are permanent.

The current medical system has not prioritized mid-life women’s health, but this is starting to change. This lack of abundant resources for women nearing or in their menopause transition is the driving force behind what we are doing at Herstasis.

Remember – it is possible to have a healthy menopause with personal perspective and a sense of control! And we’ll be with you every step of the way.

Reproductive Aging Stages

In 2001, a group of experts met with the purpose of developing a system to formally define the stages of reproductive aging. This workshop, called the Stages of Reproductive Aging Workshop (STRAW) 2 was followed in 2012 by the Stages of Reproductive Aging Workshop + 10 (STRAW+10) 3 which completed the work started in STRAW. The final results from these workshops are shown in Figure 2 below.

Reproductive: Early & Peak Stages

Learn More

Reproductive: Early & Peak Stages

STRAW+10 results divide the reproductive stage into 4 substages that are all associated with the presence of a regular menstrual cycle. It must be noted that many women have irregular cycles so the use of this tool as a generic diagnostic tool does have its limits. One suggestion from the Herstasis team is to start keeping records (even a simple checkmark in your calendar) to indicate when your period starts. This tracking method will allow you to understand more about your own cycles and will provide a good context for any discussion about menopause with your healthcare provider.

Women enter into the early reproductive stage (-5 in Figure 2) when they get their first menstrual period. The arrival of menarche is the biological signal that the female has matured to the point of being able to reproduce, although periods may be irregular during the early stage. By the peak reproductive stage (-4 in Figure 2) the menstrual cycle has stabilized and comes regularly, usually every 28 days although this is variable amongst women. [3]

Reproductive: Late Stage

Learn More

Reproductive: Late Stage

As its name implies, this is the stage when the probability of getting pregnant during one menstrual cycle starts to diminish. The STRAW+10 workshop broke this into two distinct stages, -3b and -3a. The ‘early’ late reproductive stage (-3b) sees the menstrual cycle still quite regular but some hormone levels begin to change. While FSH remains steady, AMH, which is produced in the follicles and used to estimate the number of eggs left in the ovaries, begins to decline.  [2]

The ‘late’ late reproductive stage (-3a) is characterized by changes, sometimes only subtle ones, in your periods as the flow may vary or the length of the menstrual cycle may change, usually getting shorter. [2]

Menopausal Transition: Early Stage

Learn More

Menopausal Transition: Early Stage

The biggest indicator used by clinicians to determine if you are starting the menopausal transition (stage -2) is the variability of your menstrual cycle length. If there is an ongoing change of one week or greater in consecutive cycle length, then you are considered to be formally in early menopause transition. This stage also sees elevated (but still variable) levels of FSH, lowering levels of AMH and lower numbers of follicles containing eggs. [2]

Menopausal Transition: Late Transition Stage

Learn More

Menopausal Transition: Late Transition Stage

The signal used to determine if you are in the late menopause transition (stage -1) is an absence of your period (called amenorrhea) for more than 60 days at a time. There is more variability in the length of the menstrual cycle and extreme fluctuations in hormone levels. There is also an increase in anovulation – meaning that you may still be menstruating but you are not ovulating. This stage usually lasts 1-3 years. For many women, this is when menopausal transition symptoms really become problematic. [2]

PostMenopausal: Early & Late Stages

Learn More

Postmenopausal: Early & Late Stages

Menopause itself occurs when you are completely finished with your menstrual cycles and is  diagnosed when you have not had a period for one full year. In Figure 2, it is indicated by FMP (0), meaning Final Menstrual Period. 

Once you have gone 12 months without a period, you automatically pass menopause and become postmenopausal. There are still hormonal fluctuations happening, particularly FSH and estrogen, but these hormone levels typically stabilize at two years post-menopause. [6] [7] 

Based on Figure 2, FSH and estrogen levels are still variable in stage +1a and finally stabilize in stage +1 b. Typically these stages last about 1 year each. Stage +1c continues with hormone stabilization (high FSH and low estrogen). More research is underway on how FSH and estrogen levels vary throughout the entire post-menopausal stage.  

The late postmenopausal stage (+2) marks the time when hormonal changes are no longer significant and the healthcare focus moves back to the biological clock and processes of physical aging.

Compiled References

[1] Baker FC, de Zambotti M, Colrain IM, Bei B. Sleep problems during the menopausal transition: prevalence, impact, and management challenges. Nat Sci Sleep. 2018;10:73-95 https://doi.org/10.2147/NSS.S125807

[2] Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, Woods N. Stages of Reproductive Aging Workshop (STRAW). J Womens Health Gend Based Med. 2001 Nov;10(9):843-8. doi: 10.1089/152460901753285732. PMID: 11747678.

[3] Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ; STRAW+10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. Climacteric. 2012 Apr;15(2):105-14. doi: 10.3109/13697137.2011.650656. Epub 2012 Feb 16. PMID: 22338612; PMCID: PMC3580996.

[4] Lacroix AE, Gondal H, Langaker MD. Physiology, Menarche. [Updated 2021 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470216/

[5] https://www.merckmanuals.com/en-ca/home/women-s-health-issues/biology-of-the-female-reproductive-system/menstrual-cycle

[6]  Randolph JF, Jr, Zheng H, Sowers MR, et al. Change in follicle-stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period. J Clin Endocrinol Metab. 2011;96:746–754.

[7]  Randolph JF, Jr, Sowers M, Bondarenko IV, Harlow SD, Luborsky JL, Little RJ. Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age. J Clin Endocrinol Metab. 2004;89:1555–1561.