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1MEN’S AND WOMEN’S HEALTH – SEPTEMBER 10TH, 2007

REPRODUCTIVE PHYSIOLOGY AND ENDOCRINOLOGY

 Review of menstrual cycle today. (Menstrual is just one part of it, the endometrium and ovary are cycling: this is what
we are looking at.
 Have to understand “normal” before we can discuss problems.
 Pituitary gland is secreting hormones affecting the ovary. Shedding of endometrium is the end stage of this hormone
secretion
 See chart on Pg. 2 of notes. Understand this!
 Can also add Yin/Yang and Blood/Qi cycling.
 Yin: Follicular phase: building of
 Luteal phase is more of Qi and Yang moving stage.

What are the goals of this cycle?


Procreation! Want to release 1 follicle into prepared uterus
Other theories: as detoxification process, protection.
Women are at risk of developing deficiencies, lose things in harmful fashion as well.

Hormones: classic negative feedback cycle.


The RECEPTOR is the part that affects cell activity when it binds to hormone. Different receptor determine what the cell
does.
GnRH (Hypothalamus)  pituitary gland (FSH/LH)
 Pulsatile release
 Estrogen and progesterone have negative feedback effect on GnRH
 Hypothalamus also affected by limbic system. Eg. Stress

Pituitary releases:
 FSH: maturation of follicle
 LH: release of the follicle
Prolactin is inhibitory to FSH/LH release (direct effect on pituitary gland). High during breast-feeding (lactational
amenorrhea).
Thyroid hormone: effect on pituitary release as well.
Inhibin: released by corpus luteum

Menstruation:
 Desquamation of superficial and middle layers, due to vasospasm of arterioles supplying layers of endometrium. Shed
fibrous tissue and liquid. Enzymes should be able to break down fibrous tissue completely: menstrual flow should be
liquid.
 Passage of clots gives info to ND (TCM, Homeopathy). Clots can be painful to some women.
 Necrosis due to ischemia  shedding. Leukocytes are recruited to the area of necrosis. Cervix is open to allow for
menses to pass.
 By day 4-7, endometrium has repaired itself (necrosis), and starts to build again.
 FSH is starting to rise, follicle is beginning to develop (see chart)

Proliferative phase (“Proliferative phase” refers to endometrium, “Follicular phase” refers to ovarian cycle)
 FSH has 2 peaks. Day 7, starts to promote estrogen production (this acts as negative feedback on GnRH release,
FSH release is inhibited). Drop after first peak.
 Role of estrogen: endometrium begins to build up again.
 Mucus aligns itself to allow for the passage of sperm. Mucus is thin and stretchy. Fibres are aligned in parallel
fashion.

Follicular maturation:
 Follicle has started to develop in utero.
 When FSH released, receptors on granulosa cells are activated: more layers of cells develop. Thecal cells. All cells
now surrounding follicle release estrogen. (Yin is associated with estrogen secretion)
 Estrogen up-regulates FSH and LH receptors on follicle (positive feedback mechanism)

MEN’S AND WOMEN’S HEALTH SEPTEMBER 10TH 2007 – PAGE 1


 6-12 start to develop, but usually only 1 matures and is released. 1 matures more quickly than the others, and its
estrogen shuts down FSH stimulation to others (negative feedback). This is one theory.

Ovulation occurs in response to LH surge. Surge is right before ovulation, and this is responsible for final maturation that
allows ovum to be released.

Luteal/Secretory phase
 Defined by formation of corpus luteum (CL).
 CL secretes progesterone, estrogen, inhibin. Inhibits the release of GnRH  less FSH, LH. On chart, see dramatic
drop of LH, FSH.
 (Yang is associated with progesterone secretion.) During luteal phase, there is still yin activity.
 Continued proliferation of endometrium. Lipid, glycogen content in endometrial lining.
 Progesterone: reduces uterine contractility: don’t want to expel implanted conceptus.) Placenta will take over secretion
of progesterone.
 Active secretion of hormones in this period.

Pre-menstruation:
 Beginning of involution of corpus luteum. Drop in progesterone, estrogen. FSH will start to rise a bit, even before
menstruation starts.
 Involution of structures that were stimulated by progesterone/estrogen: spiral arteries, etc…

Steroid hormones:
 Receptor in cytoplasm. Receptor complex to nucleus, affects transcription of DNA. Proteins formed as a result.
 All come from cholesterol. Note estradiol formed from testosterone metabolism
 Estriol is least active form.
 Estrogen produced in the ovaries.
 In luteal phase, lots of progesterone, some is converted into estrogen but not all of it.
 Estrogen also produced in adipose tissue, adrenal glands.

ESTROGEN

E1 = Estrone
Made in peripheral fat and in adrenals. Produced by estradiol in these tissues.

E2 = Estradiol is most active in reproductive years.


Greater receptor potential than other forms.

E3 = Estriol higher levels in pregnant women

Sex hormone binding globulin and albumin are bound to estrogens in blood stream. These are inactive: only free steroid
hormones are active.

Pictures in notes of estrogens, the circled units are the active components. Action of hormone will be based on reaction of
these active units and the receptors.
Different effects of estrogen at different body sites.

Proliferative effect on: endometrium, breast tissue, bone…


Hair growth: more stimulated by testosterone at onset of puberty.
Change in vaginal epithelium from simple cuboidal to stratified squamous: due to estrogen. Vaginal discharge composed
of sloughed epithelial cells.

Stimulatory effect on metabolism, but not as much as testosterone


Question: When women have fat removed through liposuction, will this impact their estrogen levels? Speculative answer:
probably not.

Difference between male/female skin? Female: warmer (more vascularity), softer due to estrogen influence. Increased
vascularity = increased bleeding, more heat loss (women tend to feel colder than men)

Electrolyte balance: Causes sodium retention by kidney


MEN’S AND WOMEN’S HEALTH SEPTEMBER 10TH 2007 – PAGE 2
Increased chance of thrombosis

PROGESTERONE:

Swelling of breast during luteal phase.


Progesterone has similar chemical structure to aldosterone. Competes with aldosterone for same receptors. Causes net
loss of Na+ and water, although progesterone still causes resorption of water, Na+

Estrogen ratio:
Estriol : sum of estrone + estradiol. Least potent form:sum of most potent forms
Indication of amount of estrogenic activity, and of activity of liver. Healthy ratio is 1. Protective if 1.1 or greater (more
estriol is best)

Phase 1 detoxificaiton is hydroxylation:


2-OH form: less active, more protective as it blocks activity of more active forms.
16alpha form: more active, links with estrogen dependent cancers.
2-OH : 16-OH form: best ratio is 2. (more of the 2 form)

Sample lab report: Genova Diagnostics: “alternative lab” used by NDs. We can order through the lab.
24hour urine: EstroEssence: fractionated analysis of different forms of estrogen metabolites.
Could do this if estrogen dominance is suspected.

20% of secreted estrogen metabolites is excreted through bile.


Enterohepatic circulation. Estrogen can be reabsorbed.
Factors that increase re-uptake of estrogen: bacterial content of GI, leaky gut, increased transit time.
Beta-glucaronidase: if bacteria are producing this, will undo phase 2 detoxification (glucaronidation) and release free
estrogen.

Phytoestrogen: adaptogenic.
Weaker effect on estrogen receptor than estrogen itself.
If estrogen levels are too high, phytoestrogens will occupy receptor site and will have lesser activity than endogenous
estrogen.
If estrogen levels are too low, phytoestrogens will occupy receptor site and will have more activity than endogenous
estrogen.

Sources of Phytoestrogens:
Soy: okay as whole food or fermented forms of soy. Too much soy milk, burger, etc., especially for kids, may be getting
too much estrogen activity at a time they don’t need it.
Flax: beneficial anti-estrogenic activity
Bisphenol A: leaching into our food from plastics?
“Having Faith” Sandra Steingraber. Memoires of her pregnancy and breast-feeding, and her research on the toxins
passed through breast milk. Her conclusion: breast is best.

Xenoestrogens: tend to promote the 16-OH form of estrogen.

What can we do???


Achieving a healthy body composition. Excess body fat allows for increased estrogen secretion, storage.
Healthy GI tract. Decrease transit time.
Flax! Upregulates 2-OH form of estrogen

Botanical approach?
Promote liver health: Liver herbs. Milk thistle, dandelion, Shisandra,
Hormonal regulators: Vitex (upregulates progesterone)
Alteratives: (detoxifiers). Stimulants to organs of detoxification.

Castor oil packs: “Qi-movers”


MEN’S AND WOMEN’S HEALTH SEPTEMBER 10TH 2007 – PAGE 3
Indole-3-carbonol  induces p450, promotes 2-OH form (like flax)
Found in cruciferous veggies. Steamed, not boiled.
Need 300-600mg if supplementing.

Hormone levels and emotions


Stress: cortisol produced from same precursor (cholesterol)
Effect of cortisol: inhibits hypothalamus and pituitary gland.

Liver (TCM): Liver Qi Stagnation = PMS. Lots of women have irritability, anger before period.

Limbic system: this may be another pathway through which the hormones are affected by emotions.

If you missed the assignment last class, look on e-college. Topics for research projects are also posted.

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