Cycle Variants - The Continuum
Professor-Emeritus James B. Brown
M.Sc. Ph.D. D.Sc. F.R.A.C.O.G.
A number of the types of ovarian activity reported here might be seen as being part of the development from the change from the amenorrhoea (Figure 3) of childhood through anovulatory ovarian activity (Figure 5) at menarche and the gradual maturation of the ovulatory mechanism to the eventual establishment of the fertile ovulatory cycle.
Stress of any kind is the most important factor causing ovarian activity to change from the fertile to infertile types. The change may go through stages as illustrated in Figures 12 and 13, but nothing can be predicted. Stages may skipped or reversed at random.
For the fertile woman changes are normal responsss to the environment and therefore all types of ovarian activity in the continuum can be considered to be normal.
Figures 1 to 11 have been reproduced with permission from James B Brown, 'Types of ovarian activity in women and theeeir significance: the continuum (a reinterpretation of early findings)', Human Reproduction Update, Vol 17, No 2, pp 141-158, 2011, copyright Oxford University Press.
Figure 1. A normal ovulatory cycle.
The time taken for the total fertile ovulatory process, that is, the beginning of the rapid growth phase of a follicle, its development, ovulation, formation of the corpus luteum and its demise (at menstruation), is always approximately 21 days. In a 28-day cycle it takes about 7 days for the FSH values to rise to threshold and for a follicle to commence its rapid growth phase. During these 7 days very little oestradiol is produced and the woman experiences several days of a BIP after cessation of bleeding. Many variants of the 28-day ovulatory cycle may occur.
Figure 2. A short ovulatory cycle, oestrogen values already rising on day 1.
Fully ovulatory cycles as short as 19 days have been observed. In these the oestrogen values were already rising on day 1 of the cycle showing that a follicle was developing at this time and the fertile phase had begun.
Figure 3. Amenorrhoea - no ovarian activity.
The rise in FSH production to the threshold may be delayed and this is one of the causes of lengthening of the cycle. However, the FSH output eventually rises above the threshold and the ovulatory events are set in train with the same timing as in the 28-day cycle.
A Possible Pattern
Figure 4. Several anovulatory oestrogen peaks not followed by bleeding.
In another variant, the FSH levels rise to exceed the threshold, a follicle develops but does not progress to ovulation. The developing follicle produces oestradiol. There may or may not be sufficient stimulation of the endometrium to result in an oestrogen withdrawal bleed. If bleeding does occur, this is anovulatory bleeding. Eventually a follicle develops and proceeds to a full ovulatory response. Menstruation will occur approximately 14 days later. Such transient attempts at follicular development are a cause of long cycles.
Figure 5. Constantly raised oestrogen excretion and oestrogen breakthrough bleeding.
In yet another variant, the rise in FSH production above the threshold may arrest before the intermediate level is exceeded and the follicles remain in a state of chronic stimulation. The amounts of oestradiol secreted stabilize at levels less than those of the pre-ovulatory peak. The stimulated uterine endometrium may break down as oestrogen breakthrough bleeding.
Figure 6. A correction of FSH levels, mid cycle bleeding followed by ovulation.
Usually, in the case of Figure 5, the feed-back mechanism corrects itself, the FSH values begin to rise again, they exceed the intermediate threshold and a follicle is boosted to ovulation with the same mechanisms, timings and Peak day calculation as in the 28-day ovulatory cycle. This situation is the cause of pre-ovulatory bleeding or spotting.
No LH Surge
Figure 7. Anovulatory ovarian activity with a sharp oestrogen peak followed closely by oestrogen withdrawal bleeding.
In other variants of the ovarian cycle a follicle is boosted towards ovulation but the release of LH is faulty. The boosted follicle has a limited life span, the resulting fall in oestradiol output signalling the end of the follicle's rapid growth phase results in oestrogen withdrawal bleeding. This is one form of anovulatory ovarian activity.
Figure 8. A sharp oestrogen peak followed by a luteinized unruptured follicle followed by bleeding.
In another form, some LH is released but not in sufficient amount to cause rupture (ovulation) of the boosted follicle. This is known as the luteinized unruptured follicle (LUF).
Figure 9. A luteinized unruptured follicle not followed by bleeding but followed by a fertile ovulatory cycle.
A LUF may or may not be followed by a bleed and, as in the previous variant, the next episode of ovarian activity may be a fully fertile ovulatory cycle.
Deficient Luteal Phase
Figure 10. Ovulation followed by a deficient luteal phase.
Another variation is seen when the LH surge is sufficient to cause ovulation but is insufficient to produce a fully formed corpus luteum capable of supporting a pregnancy. The cycle is ovulatory but infertile and is followed by menstruation.
Short Luteal Phase
Figure 11. Ovulation followed by a short luteal phase.
In another variation of an incomplete corpus luteum the progesterone levels rise above those seen in an LUF. They reach normal post-ovulatory values but fall prematurely so that bleeding occurs 10 days or less after ovulation. The cycle is ovulatory but infertile and is followed by menstruation.
The short luteal phase can be recognized by the shortened interval between the Peak day and menstruation
Figure 12. The continuum.
These cycle variants have been described as if they were separate entities. Actually, one merges into the next so that there is a continuous gradation from no follicular activity (amenorrhoea) through follicular activity without an LH surge (anovulatory ovarian activity), through increasing maturation of the LH mechanism up to the fully fertile ovulatory cycle. We term this the "continuum" of ovarian activity.
Increasing and Descreasing Fertility
Figure 13. Increasing and decreasing fertility.
At menarche, the first bleeding cycle is usually anovulatory and it may take several years for the full LH response to mature and fertile ovulatory cycles to commence. The reverse occurs as menopause approaches. Return of fertility after childbirth and during breast-feeding is similar to the mechanism at menarche but the time intervals between the variants are shorter. In athletes, a woman with regular ovulatory cycles frequently shows changes during times of intensive training, first to deficient luteal phases, then to LUFs, anovulation and finally amenorrhoea and then reverts back within a few months of ceasing training to fully fertile ovulatory cycles.