menstrual cycle

see also:

• gynaecology

from wikipedia:

• The length of the menstrual cycle is from the first day of menstrual flow to the day before the onset of the next menstrual flow
• variations are primarily due to variations in length of follicular phase and whether ovulation has occurred or not
• “humans are affected by the Moon's luminescence and gravimetric cycles, with the menstrual cycles aligning with the synodic month. Both light and gravity act as zeitgebers for women, with gravity likely indirectly influencing cycles through broader geophysical effects” Menstruation naturally tends to coincide with the full moon and ovulation with the New Moon as the night is darker at that time and perhaps more conducive to mating however artificial lighting has substantially reduced the Moon's luminescence effects.¹⁾

• this phase is associated with formation of ovarian follicles and eventually a dominant follicle which will rupture during ovulation
• the duration of this phase is quite variable even within the same woman but averages 13-17 days
• variability in the length of the menstrual cycle is attributed largely to variability in the length of this phase which may range from 8-29 days
• duration is longer and more variable in adolescence, then shortens and becomes more stable in the premenopausal years, it then shortens again in early perimenopause and then lengthens and becomes more variable in late perimenopause ²⁾
• it starts from the first day of menstrual flow up to the day before ovulation and involves secretion of 17-β-oestradiol from granulosa cells, formation of a dominant follicle, and proliferation of the endometrium (“proliferative endometrium”), followed by an oestradiol-peak which stimulates a spike in LH from the pituitary which is usually followed by a rupture of the dominant follicle (ovulation).

• this is the mid-cycle event where the dominant follicle ruptures to release the egg which will then travel down the Fallopian Tube to perhaps be fertilised by a spermatozoa and produce a blastocyst which will become a fetus if implantation into the uterus is successful
• this can be briefly painful in some women - this mid cycle ovulation pain is called Mittelschmertz

• this phase commences after ovulation and averages 13-14 days duration
• starts with the day of ovulation and continues until the day before the next menstrual flow and is a critical component of the menstrual cycle for fertility
• after ovulation, the corpus luteum begins making high amounts of progesterone as well as oestradiol, and this is what will help sustain a pregnancy until adequate placental activity develops
• progesterone transforms the follicular phase's proliferative endometrium into secretory endometrium in preparation for potential implantation by a blastocyst
• if pregnancy does not occur, it is followed by regression of the corpus luteum cyst and menstruation
• there is considerable variation in the duration of this phase with a range of 8-17 days although not as variable as follicular phase durations ³⁾
  • they tend to be shortest both in the first few years after menarche and in perimenopause
  • short luteal phase cycles
    • these are generally defined as being < 10 days long
    • they are associated with increased risk of osteoporosis and impaired fertility
• if ovulation does not occur, there is no luteal phase

• these are cycles of normal length which are either anovulatory or having short luteal phases
• a 2024 study of normal non-smoking white women of normal BMI with regular cycles showed that 55% of them had at least one short luteal phase cycle over a 12 month period, and 17% had at least one anovulatory cycle over that 12 month study period ⁴⁾

• age at menarche (AAM), the onset of menses in females is the age at which girls hit puberty and start having periods normally occurs between ages 10 to 15, though this has been getting earlier and earlier in recent decades.
• early puberty is linked with increased risk of a number of diseases in later life, including type 2 diabetes, cardiovascular disease, and certain cancers
• later puberty on the other hand, has been linked to improved health in adulthood and a longer lifespan
• genetic factors
  • AAM is a highly polygenic trait with over 600 genes contributing ⁵⁾
    • a receptor in the brain, known as MC3R, detects the nutritional state of the body and regulates the timing of puberty and rate of growth in children
    • other identified genes appeared to be acting in the brain to control the release of reproductive hormones ⁶⁾
    • one in 3,800 women carry variants in the gene ZNF483, which caused these women to experience puberty on average, 1.3 years later
    • six genes (including KDM4C, MC3R, TACR3 and ZNF483) have been identified which profoundly affect the timing of puberty. While these genes were discovered in girls, they often have the same impact on the timing of puberty in boys.
• role of diet and gut microbiome in puberty timing
  • in China, dietary soy protein is the primary source of vegetable protein and, as a result, may be responsible for later puberty timing in this country
    • early puberty is significantly more common in the highest tertiles of animal protein intake, which exceeds dietary recommendations.
      • 15% of the association between animal protein intake and puberty timing could be explained by the animal protein-microbial index (APMI).
    • see Nature 2024. Dietary protein sources, gut microbiome, and puberty timing in children: findings from a cohort study

• women are born with a non-renewable ovarian reserve, which is established during fetal development - the ovaries have a finite number of ovarian follicles that contain the ova
• variation in menopause timing is largely dependent on the differences in the size of the initial oocyte pool and the rate of follicle loss
• natural fertility is believed to be closely associated with menopause timing, and it declines on average 10 years before the onset of menopause
• normal variation in reproductive lifespan is causally associated with the risk of a wide range of disease outcomes, such as type 2 diabetes mellitus, cancer and impaired bone health
• when un-repaired DNA damage occurs in ova, they can die (see aging).
• the rate at which eggs are lost determines when women experience menopause
• many genes that influence the timing of menopause are likely to do this by affecting the genetic integrity of eggs - the same factors affect other cells and tissue types
• many of the genes linked to menopause timing are also risk factors for cancer
• most women reach menopause in their late 40’s to early 50’s but some do in their 30's
• premature menopause (menopause before age 45)
  • genetic factors:
    • BRCA1 and BRCA2 genes
    • CHEK2, DCLRE1A, HELB, TOP3A and CLPB
    • less common genetic mutations with large effects on timing (together they explain 10-12% of variance in menopause timing):
      • ETAA1, ZNF518A (variant found 1 in 4000 women), PNPLA8, PALB2 - if only one working gene of one of these then menopause appears to occur 2-5.5yrs earlier on average ⁷⁾
• delayed menopause
  • genetic factors:
    • SAMHD1 variant appear to result in delay of 1 year
      • the SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women