3. At the end of the class you are expected to:
Define normal menstrual cycle
Understand physiology of menstrual cycle
Know the clinical importance of normal menstrual
cycle
4. tightly coordinated cycle of stimulatory and
inhibitory effects that results in release of single
matured oocyte from a pool of hundreds of thousands
of primordial oocytes.
5. Menstrual length is 28+/- 7
days(<1% women have length <21 or
>35days)
Duration of flow is 1-8 days( average
3-5 days)
Amount of flow is 10-80 ml( average
30-50 ml)
20. BIRTH
Age from conception
No. of
germ cells
(millions)
Conception
3 6 9
months
1 10 20 40
years
Puberty
99.9% by
“Atresia”
Ovulation
(post-puberty)
Continuous loss
(Fig adapted from Johnson
& Everitt, 2000)
~7 m
~ 300,000
21. Growth and atresia of follicles are not interrupted
by pregnancy, ovulation, or periods of anovulation
This dynamic process continues at all ages,
including infancy and around the menopause
From this large reservoir, about 400 to 500 follicles
will ovulate during a woman's reproductive years
23. Menstruation
How many follicles
reach this point?
Ovulation
Lets look at follicular growth first…
There are a number of questions to ask…
Normally 1
34. 0 4 8 12 16 20 24 28
Insufficient FSH to
keep smaller follicles
going – they become
atretic.
Oestradiol
FSH
FSH
secretion
suppressed
Dominant follicle(s) can
survive.
The total duration of time to
achieve preovulatory status is
approximately 85 days
35. Granulosa cells
Theca
Androgens
LH
(Note: the production of
androgens is a normal
part of ovarian
physiology)
Androgens are
converted
(aromatized) to
oestradiol by the
granulosa cells
OESTRADIOL
(steroid)
FSH
The Two-Cell, Two-
Gonadotropin System
44. How does the LH surge
affect the follicle?
About 36 h between LH
surge and oocyte release…..
45. Oocyte:
• Completion of the 1st meiotic
division (unequal division;
extrusion of 1st polar body)
• 2nd meiotic division starts
but becomes arrested before
completion.
Loosening of cumulus cells
Microvilli across the
zona pellucida are
withdrawn.
47. • Ruptured follicle
becomes solid corpus
luteum
•has one of the highest
blood flows per unit mass
in the body
• Thecal cells and blood
vessels invade
• Granulosa cells
hypertrophy and
terminally differentiate
(“luteinisation”). Progesterone
+
Oestradiol
Steroid secretion changes –
Transformation of ruptured follicle into corpus luteum (CL)
48. 0 4 8 12 16 20 24 28
OVULATION
Oestradiol
Progesterone
What maintains
the CL?
Why does the
CL degenerate
at the end of the
cycle?
Follicular phase:
Oestradiol domination
Luteal phase:
Progesterone domination
49. Hypothalamus
Pituitary
LH
(low levels in
luteal phase)
GnRHSteroid negative
feedback keeps
LH and FSH
levels relatively
low
CL very
sensitive
CL
Progesterone
+ E2
-
-
+
Reproductive tract etc
What maintains
the CL?
52. 0 4 8 12 16 20 24 28
Menstruation
OVULATION
Oestradiol causes
an increase in
thickness (the
“proliferative
phase”)
More secretion from
the glands – hence the
term “secretory
phase”
Endometrial
depth
53. 0 4 8 12 16 20 24 28
Menstruation
Characteristic “spiral arteries”
Terminal differentiation of
stromal cells – “decidualisation”
Optimal time for
implantation
55. 1. At end of the luteal phase, steroid production declines.
2. Loss of oedema and gradual shrinking of endometrial tissue. The
spiral arteries become more highly coiled
3. Gradual reduction in blood flow to superficial layers – leading to
ischaemic hypoxia and damage to the epithelial and stroma cells.
4. 4 24 hours prior to menstrual bleeding, an intense constriction of‑
spiral arteries occurs.
5. Individual arteries re-open at different times, tearing and
rupturing the ischaemic tissues.
6. Bleeding into the cavity occurs via:
1. red cells diapedese between surface epithelial cells;
2. tears develop in the surface epithelium
3. pieces of weakened superficial endometrium crumble away
7. About 50% of degenerating tissues is resorbed and 50% is lost as
'menstrual bleeding'.
56. Probably 95% of women have
a total blood loss of less than
60 mls.
This blood loss can represent a
significant loss of iron (leading
to anaemia) – especially in
women on marginal diets
57. Menstruation - WHY?
In preparation for pregnancy, the human uterine stromal
cells go through complex changes and the stromal cells
terminal differentiate - “Decidualization”.
If implantation and pregnancy do not occur, this tissue is
lost - and the uterus prepares itself again for another
possible pregnancy.
58. Probability of clinical pregnancy following intercourse on a given day
relative to ovulation (estimated from basal body temperature).
Day of intercourse Ovulation?
Nearly all
pregnancies
in a 6-day
fertile window
59. 0 4 8 12 16 20 24 28
Menstruation
OVULATION
Cervical
mucus
Variable
number of
“dry” days
Production
of low
viscosity
mucus
increases
Abundant mucus
- like “raw egg
white”
Thick, rubbery, high
viscosity -
impenetrable to
sperm.
60. With increasing oestradiol:
1. The mucus becomes more
abundant - up to 30x more and
its water content increases.
2. Its pH becomes alkaline.
3. Increased elasticity –
("spinnbarkeit test")
5. “Ferning pattern” caused by the
interaction of high concentrations
of salt and water with the
glycoproteins in the mucus.
Characteristic fernlike pattern as
the mucus dries on a glass slide.
61. 0 4 8 12 16 20 24 28
Menstruation
OVULATION
LH
36
36.2
36.4
36.6
36.8
37
37.2
37.4
37.6
37.8
38
A small (0.5 o
C) rise
in BBT typically
follows ovulation.
Basal body temperature
63. Basal body temperature
Plasma oestradiol
Plasma progesterone
Volume of cervical mucus
– and sperm penetration
Uterine endometrium
64. a) Calendar Method - which is essentially
based on the previous menstrual history.
b) Temperature method - using a midcycle
rise in body temperature as a sign when
ovulation has occurred.
c) Cervical changes - which can be detected
by feeling the cervix and cervical mucus.
d) Hormonal methods - using over-the-
counter "kits" to assess urinary hormone
levels.
There are a number of potential ways of trying
to identify the “fertile” period..:
65. Follicular phase estrogen production is explained by the
two-cell, two-gonadotropin mechanism, allowing the critical
creation of an estrogen-dominated microenvironment.
Selection of the dominant follicle is established during days
5 to 7, and consequently, peripheral levels of estradiol begin
to rise significantly by cycle day 7.
66. Estradiol levels, derived from the dominant follicle,
increase steadily and, through negative feedback
effects, exert a progressively greater suppressive
influence on FSH release.
While directing a decline in FSH levels, the
midfollicular rise in estradiol exerts a positive
feedback influence on LH secretion
67. A unique responsiveness to FSH allows the
dominant follicle to utilize the androgen as
substrate and further accelerate estrogen
production.
FSH induces the appearance of LH receptors on
granulosa cells
The LH surge initiates the continuation of meiosis
in the oocyte, luteinization of the granulosa, and
synthesis of progesterone and prostaglandins
within the follicle
68. 1. Williams obstetrics, 24th
edition
2. Williams Gynecology, 2nd
edition
3. Gabbe, Normal and problem pregnancies, 6th
edition
4. Uptodate, 21.6
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
OK, so the control of the oestrous cycles has to be seen from a very broad perspective - but lets focus in a bit and see what we can say about the general principles on which the variability is based.
This synchronisation is between many parts of the body…..
Ovary, uterus, oviduct, brain, vagina….
And is achieved by hormones! - very dynamic
Note the delay between the high steroid levels and oestrus! Remember while we use criteria to follow cycles, these are just convenient reflections of what is happening internally
Also, in terms of hormones, you have to remember that these are the circulating signals - not an end in themselves. The important thing is how the tissues respond - and in terms of the response we have to consider three things:
a) level of hormone may affect different tissues differently(in sheep, with low levels of e2 the LH surge and mating are not particularly closely synchronized, while high levels produces high level of synchronization)
b) time for response - eg. E2 induces mitoses… cornification in vagina at oestrus AFTER peak of e2
c) profile that matters - interactions between P and e (e.g. implantation window)
In rats, pattern of T and androstenedione mirror e2
Dominant progestin is 20 alpha OH-P - from newly formed CL
