Menorrhagia

The pathophysiology of abnormal uterine bleeding (AUB) is as diverse as the classification of the disease.
AUB can be caused by pelvic pathology like a distortion of the endometrial cavity due to fibroids, or
endometrial protrusions into the cervix or vagina (polyps), or because of friable endometrial tissue. The
friable endometrial tissue is likely caused by unopposed estrogen which causes the endometrium to
become friable, vascular, and lacking sufficient stromal support which equates to heavy, continuous
uterine bleeding.
Systemic conditions are also responsible for AUB. Obesity is an epidemic whose consequences affect
every aspect of life and every organ system. In women, obesity can lead to unopposed estrogen and can
lead to the polycystic ovarian syndrome (PCOS). Coagulopathies can also lead to AUB; 13% of women
with AUB have a variant of Von Willebrand disease, and 20% have an some underlying coagulopathy.
Another important consideration and a significant cause of AUB are the patient’s medications. An intact
coagulation pathway is essential for menstrual regulation and medications that interact with platelets and
coagulation factors can lead to Acute AUB. The following is a list of some medications that can lead to
AUB: Warfarin, aspirin, clopidogrel, and other anticoagulants; Conceptive medications and devices;
Tamoxifen; Tricyclic antidepressants; Antipsychotics; Corticosteroids
Menorrhagia
Causes
Adenomyosis

Adenomyosis is defined as the presence of ectopic endometrial glands and endometrial functionalis lining in the myometrium.

Reduced apoptosis (programmed cell death) and increased proliferation of the eutopic endometrial lining could play a role in
the pathophysiology

Increased synthesis of estrogen due to increased aromatisation, and possibly progesterone resistance due to reduced
progesterone receptor

Increasing parity, termination of pregnancy, uterine curettage, and caesarean birth --- all may disrupt the endo-myometrial
junction and thereby allow infolding of the endometrium with direct myometrial invasion.

There also appears to be an association with estrogen exposure. Increasing age with increased duration of estrogen exposure,
and tamoxifen use positively correlate with adenomyosis risk

Other gynecological conditions that may be associated include uterine fibroids and endometriosis

Diagnosis of adenomyosis is based on histology (at hysterectomy) and imaging. The common imaging modalities used for
non-histological diagnosis of adenomyosis include TVUS and MRI, although a clear consensus on imaging criteria remains
lacking.
Menorrhagia
Causes
Uterine fibroids (myomas, leiomyomas) are the most common benign tumors in women of reproductive age present in almost
80% of all women by the age of 50. Fibroids tend to be twice or even three times more common in black women

Fibroids are steroid hormone-dependent tumors

The association between AUB and fibroids is complex and poorly understood, as women with fibroids may be asymptomatic.

The proposed mechanisms of how fibroids may cause AUB include an increase in the endometrial surface, an increase in uterine
vascularization, changes in patterns of myometrial contractility, ulceration of the surface of a myoma and uterine venous ectasia
by compression effect from the myoma(s)

Endocrine-disrupting chemicals (EDCs) are substances in environment, food, and consumer products that interfere with hormone
biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction and there is evidence
to suggest that exposure to EDCs, especially in critical phases of uterine development such as in utero and early childhood, may
result in genetic mutations influencing fibroid growth

There is a correlation between AUB and the degree of distortion and penetration of the uterine cavity. Submucous myomas are
thought to be most symptomatic. Distortion of the uterine cavity by fibroids is also proposed to explain other symptoms such as
infertility

An impairment of maturation and differentiation of lymphocytes in women with large leiomyomas suggested a decrease in the
local immune response
Menorrhagia
Causes
Ovulatory disorders

Anovulation is observed at extremes of age. Also with endocrine disorders such as hypothyroidism,
PCOS, , hyperprolactinemia and with factors such as mental stress, extremes of weight change,
excessive exercise, and even drugs that interfere with HPO axis such as dopamine agonists.

PCOS is the most common cause of infertility in women in this category. India reported a
prevalence of 3.7% to 22.5%, upto 36% prevalence in adolescents

Anovulatory cycles may contribute to AUB by unopposed oestrogen effects on the endometrium
causing marked proliferation and thickening resulting in HMB along with an altered frequency of
menstruation.
Menorrhagia
Causes
Ovulatory disorders

PCOS

During an anovulatory cycle, there is low progesterone because the corpus luteum does not form
(luteal phase defect). Thus, the normal cyclical secretion of progesterone does not occur, and
estrogen stimulates the endometrium unopposed. The endometrium continues to proliferate,
eventually outgrowing its blood supply; it then sloughs incompletely and bleeds irregularly and
sometimes profusely or for a long time. When this abnormal process occurs repeatedly, the
endometrium can become hyperplastic, sometimes with atypical or cancerous cells. In such cases,
the menstrual cycle may be shortened too.
 PCOS

Imbalance between androgens and FSH, cause a halt of follicular growth.

Elevated insulin levels are present in about half of these patients and are correlated to BMI, but not all PCOS patients are insulin
resistant

High insulin levels increase testosterone production by over stimulating the theca cells to produce more estrogen which lead to
premature follicular atresia and even anovulation

High insulin causes low levels of sex hormines binding globulin SHBG (produced in liver) which is not able to bind with
testosterone & estrogen leading to again high hormones.

This, together with an increase in peripheral production of estrogens may give negative feedback to hypotghalamus to not
produce GnRH .

Visceral adiposity in PCOS is associated with increased IR, leading to exacerbation of reproductive and metabolic abnormalities.
In turn, androgens promote visceral fat accumulation and IR by inhibiting lipolysis and promoting lipogenesis.
 Menorrhagia
Causes
Ovulatory disorders

PCOS

High LH prematurely luteinize

granulosa cells. LH also AMH is secreted by the pre-antral & small
stimulates luteinized granulosa antral follicles measuring ≤4 mm & ceases
cells to secrete estradiol, which when follicle size reaches ≥10 mm
suppresses FSH secretion.

Breakthrough bleeding
PCOS

Risk factors- Consumption of high energy food items,

obesity, lack of physical activity, family history and
gestational DM

During puberty, there may be a temporary increase in

insulin levels and IR.

Complications- Infertility, other metabolic disorders

and cancers
PCOS (lean and obesity)

Presentation-

Excessive testosterone-
● Virilization - excessive hair growth on chin, upper lips, chest and back
(hirsutism), thinning of hair from crown of scalp, and acne on face, chest and
back
● Anovulation - amenorrhea and hypomenorrhea- sub/infertility

Insulin resistance-
● Overweight/obesity and acanthosis nigricans
 PCOS (lean and obesity)

LEAN VS OBESE PCOS

Weight gain and central obesity, although not a diagnostic criterion, are common features of PCOS. obesity
significantly impacts the PCOS phenotype since it is associated with a higher prevalence of menstrual irregularity,
hyperandrogenemia, and hirsutism

Obese individuals with PCOS suffer from more severe hormonal and metabolic derangements compared to their
lean counterparts

There were also no differences in clinical manifestations of PCOS between the lean and overweight subgroups,
such as hirsutism, hyperandrogenism and findings from pelvic ultrasonography. Recent studies therefore indicate
that hormonal profiles and insulin resistance with resultant hyperinsulinaemia are similar in both phenotypes of
PCOS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405408/#:~:text=Although%20a%20majority%20of%20cases,are%20termed%20as%20lean
%20PCOS.
Menorrhagia
Causes
Ovulatory disorders

PCOS
Menorrhagia
Causes
Ovulatory disorders

PCOS
PCOS (lean and obesity)
PCOS (lean and obesity)
PCOS (lean and obesity)
 PCOS (lean and obesity)

Constant LIFE STYLE therapy for this lifestyle disorder. Don’t be couch potato
https://www.facebook.com/healthspecificsphysio/photos/a.119984312863834/447218996807029/
PCOS (lean and obesity)

There is no differences in clinical manifestations of PCOS between the lean and overweight subgroups, such as
hirsutism, hyperandrogenism and findings from pelvic ultrasonography.

Recent studies therefore indicate that hormonal profiles and insulin resistance with resultant hyperinsulinaemia
are similar in both phenotypes of PCOS.

Still obese individuals with PCOS suffer from more severe hormonal and metabolic derangements compared to
their lean counterparts

Anovulation is a more probable occurrence in obese rather than thin individuals with PCOS

Weight loss is considered first-line treatment in women exhibiting the obese phenotype of PCOS, but this is not
considered in lean women with the syndrome . Caloric restrictions are unnecessary as lean women may not
necessarily be required to lose weight. Instead lean PCOS women should aim to maintain their weight. Lifestyle
modifications by dietary interventions and regular physical activity have demonstrated improved insulin
resistance and ameliorated hyperandrogenism amongst other beneficial effects on PCOS symptoms Lean
individuals with PCOS must be encouraged to consume vegetables and fruit to ensure they are having an
adequate supply of various minerals, vitamins and nutrients.
Menorrhagia

Causes

Coagulopathy
Coagulopathies are reported to affect 13% of the women presenting with HMB. Structured history for
coagulopathy screen. Adapted from Koudies et al.-

1. Heavy bleeding since the menarche

2. One of the following:

•
Postpartum haemorrhage
Surgical-related bleeding
Bleeding associated with dental work

3. Two or more of the following:

•
Bruising 1–2 times/month
Epistaxis 1–2 times per/month
Frequent gum bleeding
Family history of bleeding problems
Menorrhagia

Causes

Iatrogenic
Exogenous steroids, usually as continuous estrogen and or progesterone therapy results in unscheduled
bleeding.
Drugs that interfere with ovarian steroid release may have a similar effect (GnRH agonists and
antagonists) and aromatase inhibitors. The use of IUD may contribute to chronic endometritis and AUB.

A structured history and examination and exclusion of other causes help to secure the diagnosis. Often
cessation of the drug or removal of the device (implant, intrauterine device) helps resolve the problem.

Fibroids and polyps

Fibroids are noncancerous growths that form from the muscle tissue of the uterus. Polyps are another
type of noncancerous growth. They can be found inside the uterus or on the cervix. Both can cause
irregular or heavy menstrual bleeding.

Not other specified causes

AVMs,, endometrial pseudoaneurysms, myometrial hypertrophy and uterine isthmocele
Menorrhagia

Causes
AUB-E

AUB that occurs in the context of a structurally normal uterus with regular menstrual cycles without
evidence of coagulopathy is likely to have an underlying endometrial cause.

Hypoxia, inflammation, haemostasis and angiogenesis all play crucial roles in the shedding and
subsequent scarless repair of the functional upper layer of the endometrium. Perturbation of local
glucocorticoid metabolism, aberrant prostaglandin synthesis and excessive plasminogen (resulting in
premature clot lysis) have all been implicated in AUB

AUB-E may be implicated in many women with AUB, but a lack of clinically available specific tests or
biomarkers means that practical testing for such disorders is not yet feasible. As such, diagnosis depends
on careful history taking and exclusion of other contributors. The high prevalence of potential
endometrial dysfunction means that it is highly likely that those with AUB-L will often have an element
of AUB-E contributing to increased/aberrant menstrual blood loss with its attendant implication for
therapy.
Menorrhagia
AMENORRHEA (Absence of menstruation)/HYPERMENORRHEA (less frequent menstruation)

Normal before menarche, during pregnancy, during lactation and post-menopause (adv to use
contraception until she has no periods for 12 months in row)
Most amenorrhea, particularly secondary amenorrhea, is anovulatory. Anovulatory amenorrhea
occurs when part of endocrine system does not function well.

However, amenorrhea can occur when ovulation is normal such as in genital anatomic
abnormalities (eg, congenital anomalies causing outflow obstruction, intrauterine adhesions)
prevent normal menstrual flow despite normal hormonal stimulation.

Primary amenorrhea is failure of menses to occur by age 15 years in patients with normal
growth and secondary sexual characteristics. The presence of normal secondary sexual
characteristics usually reflects normal hormonal function (and the reason may be obstructive
pathology) and if accompanied by abnormal secondary sexual characteristics is usually
anovulatory (eg, due to a genetic disorder).
Amenorrhea/Hypomenorrhea

Secondary amenorrhea is for the length of 3 cycles after the establishment of regular menstrual
cycles.
Galactorrhea suggests hyperprolactinemia (eg, pituitary dysfunction, use of certain drugs); if visual
field defects and headaches are also present, pituitary tumors should be considered.
Symptoms and signs of estrogen deficiency (eg, hot flushes, night sweats, vaginal dryness or
atrophy) suggest primary ovarian insufficiency (premature ovarian failure) or functional
hypothalamic anovulation (eg, due to excessive exercise, a low body weight, or low body fat)

Virilization and clitoral enlargement suggest androgen excess (eg, polycystic ovary syndrome,
androgen-secreting tumor, Cushing syndrome, use of certain drugs). If patients have a high BMI,
acanthosis nigricans, or both, PCOS is likely.

Complications of amenorrhea-

Infertility, Osteoporosis, Psychological distress, Others related to the etiology

Hyperprolactinemia induces the suppression of hypothalamic Kiss1
Amenorrhea/Hypomenorrhea
neurons that directly control the pulsatile release of GnRH.
Amenorrhea/Hypomenorrhea
POF-Premature Ovarian Failure
Amenorrhea
 MANAGEMENT APPROACH OF BEFORE ● Unpredictable cycle length
PERIMENOPAUSAL DUB
● Unpredictable bleeding pattern
● Regular cycle length ● Frequent spotting
● Presence of ● Infrequent heavy bleeding
premenstrual ● Monophasic temperature curve
symptoms
● Dysmenorrhea
The first step in identifying the etiology of abnormal
● Breast tenderness uterine bleeding is to determine the patient's ovulatory
● Change in cervical status.
mucus
Anovulation is the most common cause of DUB in
● Mittelschmerz reproductive-age women and is especially common in
● Biphasic temperature adolescents.
curve
Up to 80 percent of menstrual cycles are anovulatory in
● Positive result from use
the first year after menarche. Cycles become ovulatory
of luteinizing-hormone an average of 20 months after menarche.
predictor kit
If anovulatory bleeding is not heavy or prolonged, no
Another cause of anovulation is polycystic ovarian disease, treatment is necessary. If the adolescent is distressed
which is usually associated with obesity, increased circulating by the irregularity of her menses or has been
androgens and insulin resistance. Excess androgens are anovulatory for more than a year, oral contraceptive
converted to estrogen in peripheral tissues. This unopposed pills are the treatment of choice.
estrogen state increases the risk of endometrial hyperplasia
and cancer. Some women with chronic anovulation do not fall
into any of the above categories and are considered to have
idiopathic chronic anovulation. Some women still have anovulatory cycles after the
hypothalamic-pituitary axis matures. Serum levels of
All causes of anovulation represent a progesterone-deficient thyroid-stimulating hormone and prolactin should be
state. Treatment options include exogenous progesterone measured to exclude significant pathology. Weight
every three months to protect against endometrial cancer, oral loss, eating disorders, stress, chronic illness or
contraceptives or, if pregnancy is desired, ovulation induction excessive exercise may all cause hypothalamic
with clomiphene (Serophene). If not better, referral. (OCP Can
be contd until menopause, after that HRT anovulation.
https://www.aafp.org/pubs/afp/issues/1999/1001/p1371.html#afp19991001p1371-f1
 MANAGEMENT APPROACH OF BEFORE PERIMENOPAUSAL DUB (contd.)
● Regular cycle length
● Presence of premenstrual symptoms
● Dysmenorrhea
● Breast tenderness
● Change in cervical mucus
● Mittleschmertz
● Biphasic temperature curve
● Positive result from use of luteinizing-hormone predictor kit

Although less common than anovulatory bleeding, ovulatory DUB may also
occur. DUB in women with ovulatory cycles occurs as regular, cyclic bleeding.
Menorrhagia may signify a bleeding disorder or a structural lesion, such as
uterine leiomyomas, adenomyosis or endometrial polyps. Up to 20 percent of
adolescents who present with menorrhagia have a bleeding disorder such as
von Willebrand's disease.3 Liver disease with resultant coagulation
abnormalities and chronic renal failure may also cause menorrhagia.

Polymenorrhea is usually caused by an inadequate luteal phase or a short

follicular phase. Oligomenorrhea in an ovulating woman is usually caused by
a prolonged follicular phase. Intermenstrual bleeding may be caused by
cervical disease or the presence of an intrauterine device. Midcycle spotting
may result from the rapid decline in estrogen levels before ovulation.1

An endometrial biopsy should be considered early in the evaluative process

of women who have a history of prolonged exposure to unopposed estrogen,
who do not respond to initial management strategies or who are over age 35.
PERIMENOPAUSAL DUB- APPROACH

As women approach menopause, cycles shorten and often

become intermittently anovulatory. These changes are the
result of a decline in the number of ovarian follicles and in the
estradiol level. As follicles decrease in number, the level of
follicle-stimulating hormone needed to stimulate ovulation
increases.

EXCLUDING ENDOMETRIAL CARCINOMA

All perimenopausal women with persistent AUB should be
evaluated for the presence of endometrial hyperplasia or
carcinoma.

Endometrial biopsy is the most widely used.

In women with normal findings on biopsy, treatment usually

consists of monthly progesterone withdrawal or low-dose OCP.

Usually, the estrogen dose in HRT is not sufficient to stop

bleeding from an atrophic endometrium, and higher doses of
estrogen are typically necessary
MANAGEMENT APPROACH OF BEFORE PERIMENOPAUSAL DUB
MANAGEMENT APPROACH OF PERIMENOPAUSAL DUB
MANAGEMENT APPROACH OF POSTMENOPAUSAL DUB
Menstrual Abnormalities That May Require Evaluation (ACOG)
Menstrual periods that

● have not started within 3 years of thelarche

● have not started by 14 years of age with signs of hirsutism

● have not started by 14 years of age with a history or examination suggestive of excessive exercise or eating disorder

● have not started by 15 years of age

● occur more frequently than every 21 days or less frequently than every 45 days

● occur 90 days apart even for one cycle

● last more than 7 days

● require frequent pad or tampon changes (soaking more than one every 1–2 hours)

● are heavy and are associated with a history of excessive bruising or bleeding or a family history of a bleeding disorder
 4. ROLE OF HORMONES IN
MAMMOGENESIS & LACTOGENESIS
Mammary gland development is highly dependent on the actions of hormones, including estrogen and progesterone,
and these endocrine factors act locally within the tissue through complex interactions with growth factors and
cytokines in the mammary microenvironment

Endocrine system plays a major role in synchronizing development (mamogenesis) and function (lactogenesis)

Three categories of hormones:

Reproductive hormones (endocrine)- Estrogen, progesterone, prolactin, oxytocin
Metabolic hormones (endocrine)- GH, corticosteroids, thyroxin, PTH and insulin
Mammary hormones (autocrine)- GH, prolactin, PTHrP (Parathyroid hormone-related protein) and leptin

During puberty
*The lobules are the glands that
Progesterone stimulate development of lobules* produce milk. The ducts are
Estrogen stimulate proliferation of ducts* and deposition of fat tubes that carry milk to the
nipple.

(Complete development of lobules happens during pregnancy)

Although estrogen and progesterone are essential for physical development of the breasts, they inhibit actual
secretion of milk. Prolactin’s level increases 10-20 times during pregnancy for the milk production, while there is
sudden drop in estrogen and progesterone after delivery allows milk production

Oxytocin, produced at the end of the pregnancy by the brain and the placenta, induces contractions and assists in
milk production

Suckling stimulates further increase in expression of genes involved in milk secretion

with expansion of alveolar epithelium. Lactation is maintained by removal of milk
in which 2 hormones involved namely Prolactin (milk production) & Oxytocin
(milk let-down)

By sucking at the breast, baby triggers tiny nerves in the nipple.

These nerves cause hormones to be released into bloodstream.
One of these hormones (prolactin) acts on the milk-making tissues.
The other hormone (oxytocin) causes the breast to push out or ‘let down’ the milk.

USE IT OR LOSE IT
A BIT OF BREAST CANCER
A BIT OF BREAST CANCER
RISK FACTORS

Early age (<12) at menarche and late age (>55) at menopause:

A number of studies suggest that the mammary gland is more susceptible to carcinogenesis when there is higher
proliferative activity in mammary epithelial cells

Risk of developing breast cancer increased in both pre-and post-menopausal patients who had early onset of
menarche and late menopause possibly due to the increase in the duration of hormonal exposure.Risk increases
linearly with the cumulative number of ovulatory cycles. Proliferation of breast epithelium in the luteal phase
increases the risk of promotion of initiated cells.

Main proliferative phase is the mid-luteal phase of the menstrual cycle, during which time circulating
progesterone and estrogen are both high and epithelial alveolar buds begin to form.

For each year younger a girl commences menstrual cycling, there is a 5% increase in lifetime risk of breast cancer.
Similarly, for each year older at the time of menopause, there is a 3.5% increased breast cancer risk. Studies on
naturally postmenopausal women also showed increased breast cancer risk in those who had experienced greater
than 490 menstrual cycles in their lifetime as compared to those with fewer or irregular cycles. This indicates that
fluctuations in ovarian hormones associated with menstrual cycling affect breast cancer susceptibility.
A BIT OF BREAST CANCER
RISK FACTORS

Late age (>35) of first full-term birth and nulliparity:

Pregnancy both promotes and protects against breast cancer. All parous women are under a 10–30% increased risk of
developing breast cancer for at least a decade after childbirth in comparison to nulliparous young women, with older
age at first birth increasing the magnitude of risk

Late age at first full-term birth and nulliparity increase time for exposure to carcinogens.

The breast undergoes proliferation and differentiation during pregnancy, in preparation for lactation.

Terminal differentiation of the terminal ductal lobular unit (TDLU) occurs in the final trimester; this is hypothesized
to be an important mechanism linking full-term pregnancy to long-term reduced risk of breast cancer, shielding the
breast tissue from carcinogenic transformation

However, pregnancy itself causes a transient risk of breast cancer because of increased estrogen and progesterone
exposure.

In addition, pregnancy and breastfeeding, which both reduce a woman’s lifetime number of menstrual cycles, and thus
her cumulative exposure to endogenous hormones, are associated with a decrease in breast cancer risk.
A BIT OF BREAST CANCER

Increasing number of births and spacing:

Risk of declines with the number of children borne. Some evidence indicates that the reduced risk associated
with a higher number of births may be limited to hormone receptor–positive breast cancer. In addition, the
spacing between births can influence breast cancer risk, with less than 1 year or greater than 3 years providing
more protection than a birth space of 1–2 years

Previous breast cancer incidence models show that increasing spacing between the 1st and 2nd child birth
increases the overall breast cancer risk. Russo & Russo suggested that though the breast exhibits maximum
differentiation after the first pregnancy, not all tissue might have been fully differentiated. A close second
pregnancy further differentiates breast cells and therefore offers less time to accumulate DNA damage

postmenopausal women showed no increase in risk of ductal and lobular breast cancer for short birth interval
categories seems to confer to the long term protection due to terminal differentiation of mammary glands

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5404-z
A BIT OF BREAST CANCER

Breastfeeding
Breastfeeding is considered to have a protective effect against breast cancer risk by aiding the differentiation of
mammary epithelium in its terminal phase. The protection gained from breastfeeding could also be due to long-
term endogenous hormonal change, i.e., decreased estrogen and increased prolactin levels, thus, inhibiting
initiation and growth of breast-cancer cells

Several studies have shown an inverse association. It could be hypothesized that GM women with short
intervals between the 1st and 2nd birth might have breastfed their children for only a short time. It is possible
that in premenopausal women, part of the increase in ductal breast cancer risk observed in connection with a
short interval below one year between the 1st and 2nd birth is defective breast maturation owing to a lacking or
short breastfeeding period, and possibly also a lack of prolactin effect
A BIT OF BREAST CANCER

Post-lactational inoculation:
Post-pregnancy and post-lactation, the breast undergoes involution. Involution* has features of wound healing.
Breastfeeding delays the process of involution increasing the risk of cancer

*Involution is epithelial cells rapidly undergoing programmed cell death and the remaining cells are remodeled into a
glandular structure that resembles the prepregnant state.

In postpartum patients, a ~3-fold increase in liver metastasis. Postpartum liver is found to support breast cancer
metastasis. This appears to be due to a functional link between the mammary gland and liver that is established
to support lactation. Specifically, in preparation for lactation and throughout lactation, the rodent liver doubles
in size and increases anabolic metabolism. Upon weaning, the liver undergoes a regression process that
displays the hallmarks of mammary gland involution
A BIT OF BREAST CANCER

Aging: Risk increases with advancing age. Risk at age 40 is 1:217 and risk at age 80 is 1:10 because the longer
we live, there are more opportunities for genetic damage (mutations) in the body. And as we age, our bodies
are less capable of repairing genetic damage.

Smoking: First hand smoking at a young age as well as before a first full term pregnancy. Smoking allows
tobacco carcinogens to initiate breast cells prior hormonal stimulation during young adulthood and pregnancy.
Cigarette smoke contains at least 20 carcinogens that are known to transform breast cells.

Affected first-degree relatives: Risk increases with number of affected relatives, especially with early-onset
breast cancer, bilateral breast cancer or male breast cancer.

Alcohol: Alcohol has been shown to increase the amount of circulating estrogen, possibly by decreasing
hepatic metabolism, increasing aromatase activity, or increasing adrenal sex hormone production.
A BIT OF BREAST CANCER

Hormone replacement therapy (HRT): Combined estrogen and progesterone therapy has been linked to the
development of breast cancer in postmenopausal women; not estrogen alone. ACTUALLY MIXED RESULTS!

OCP do not increase risk.

HRT likely promotes preneoplastic lesions rather than initiate them. https://www.ncbi.nlm.nih.gov/books/NBK234348/

Exercise: Exercise, while a powerful tool, is not going to be enough to prevent breast cancer entirely. It is just one pillar
of a healthy lifestyle that can reduce risk

A meta-study of 2014 revealed that women could significantly reduce the risk of obtaining breast cancer by an average
of 25% if they exercise regularly

PA (physical activity) helps to lower the level of circulating hormones (principally oestrogen, leptin and insulin) and
related growth factors such as IGF-1, and reduces levels of chronic inflammation markers like CRP which can
contribute to cancer development and progression. It also enhances the immune system and decreases oxidative stress.

Research shows that women who exercise the equivalent of walking 3 to 5 hours per week at an average pace after
being diagnosed with breast cancer may improve their chances of surviving the disease.
A BIT OF BREAST CANCER

Precocious puberty & early Menarche:

The longer a woman menstruates, the higher her lifetime exposure to the
Involution is epithelial
hormones.
cells rapidly
undergoing
Also here hypothesis is that the earlier the surge of estrogen signaling at programmed cell
puberty, the earlier the start of rapid proliferation of mammary cells to generate death and the
the ductal tree and the more time the mammary gland has to accumulate these remaining cells are
mutations that ultimately lead to tumor formation. remodeled into a
glandular structure
that resembles the
Ionizing radiation: Breast tissue is sensitive to carcinogenic effects of
prepregnant state.
radiation. Risk is highest in the developing breast and absent after menopause.
A BIT OF BREAST CANCER

Bowel habits: Results suggest a slight increased risk of breast cancer for both decreased frequency of bowel
movements and firm stool consistency. https://www.facebook.com/healthspecificsacademy

Diet: No food or diet can prevent from getting breast cancer. But some foods can make body the healthiest it can be,
boost the immune system, and help keep risk for breast cancer as low as possible.

Breast cancer is less common in countries where the typical diet is plant-based and low in total fat (polyunsaturated fat
and saturated fat).

One study suggests that girls who eat a high-fat diet during puberty, even if they don't become overweight or obese, may
have a higher risk of developing breast cancer later in life.

More research is needed to better understand the effect of diet on breast cancer risk. But it is clear that calories do count
-- and fat is a major source of calories. High-fat diets can lead to being overweight or obese, which is a breast cancer
risk factor because the extra fat cells make estrogen, which can cause extra breast cell growth. This extra growth
increases the risk of breast cancer.

Other risk factors ( and Category of modifiable & non-modifiable) :

https://www.facebook.com/herpreventionandrehab/photos/a.103639352064662/106357521792845/
 5. EFFECT OF
MENSTRUATION ON BODY
SYSTEMS & VICE-VERSA
(The Hormonal Horoscope/
The Biohacks)
Learning how your hormones impact you week to week isn't just interesting, it's a vital part of managing your health.
Learning how my hormones impact me week to week isn't just interesting, it's a vital part of managing my
health & helps me provide better self-care.

I know based on where I am in my cycle what unique needs I have.

For example, in my Week 1, I know to avoid migraine triggers because I'm more susceptible. In my Week
2, I remind myself to eat and take breaks because I can become a workaholic and i can indulge in high
intensity exercises. In my Week 3, I build naps into my schedule to combat fatigue. In my Week 4, I use
positive affirmations to counter negativity.

Hormone awareness helps me be healthier and happier every day of my cycle.

I want that for you, too.

I can't guarantee that every day of your menstrual cycle is going to be a great one. But, I can guarantee
that by learning more about how your hormones impact your moods, health and behavior, you at least
have a shot at making each cycle day a little better.

So, let’s learn with me about the hormone’s programming.

Blood sugar levels

Progesterone is studied to be causing insulin resistance in muscles, impaired beta-cells proliferation and insulin
release.

● During ovulation when progesterone is high and late luteal phase both estrogen and progesterone are high,
blood sugar (BS) is high. However, levels comes normal often after periods start.
● Progesterone also causes food craving for simple carbohydrates that too with natural tendency to remain
inactive during premenstrual & periods timing which can further contribute to poor glycemic control
● This phenomenon is aggravated in case of high BMI, PMS, exogenous hormones and pre-menopause.
Diabeteic females with smoking should avoid OCP. PCOS female are at a particularly high risk of insulin
resistance, type 2 diabetes. Also uncontrolled BS is risk factor for vaginal yeast infections (candidiasis- a
fungal infection) as yeast feeds on sugar

● High estrogen levels (as in the preovulatory phase) enhances insulin sensitivity and action while lower
estrogen levels ((as in the follicular phase) and higher progesterone levels (as in the mid-luteal phase)
favours insulin resistance.
Blood sugar levels

Day 1-10: May experience higher blood sugars and insulin resistance on the first day, but insulin sensitivity should
revert back to normal for the rest of period, and a few days after it ends.

Day 11 - 14: Periovulation (i.e. when ovulating), so may experience higher (and somewhat erratic) blood sugar
levels and insulin resistance once again. When body is prepping to release an egg, the levels of LH, FSH and
estrogen all rise, which can cause a spike in your blood sugar lasting 2-3 days, max.

Day 15 - 20: The blood sugar level drops closer to its typical level for a few days.

Day 21 - 28: … and up we go again! This is the point in cycle, known as the mid-luteal phase, where more likely to
experience significant insulin resistance and higher blood sugar levels in the days before start of next period. And
then the cycle begins all over again!
Blood sugar levels

● Keeping the BS under control throughout the month can stabilize the premenstrual BS instability and
potential dehydration. Type 1 DM is more sensitive to these hormonal changes
● Limit intake of alcohol, chocolate and caffeine, as these can affect mood and increase the likelihood of
reaching for the high-carb, high-sugar treats
● Have regular, set meal times and avoid snacking throughout the day
● If do need a snack, stick to low-fat, low-carb treats that are less likely to spike BS
● Do regular exercise throughout the month to decrease blood glucose levels and manage mood
● Alternate of OCP for PMS, contraception, menstrual disorders and HRT for premenopause if h/o high
BS/DM and smoking
● Keep track
● Keep insulin and other meds nearby (beware of hypoglycemia)
● May need to lower the meds and insulin dosages on other days
● Prophylactic monitoring and lifestyle modifications in case of family history, high BMI, ETC.
Exercise & Sports

Hormones influence the specificities of female physiology, from cardiovascular to autonomic nervous systems,
thermic stress responses (Hashimoto et al., 2014; Barnes and Charkoudian, 2021) or energetic metabolic pathways
(Tarnopolsky, 2008; Fu et al., 2009), and even cell-mediated immunity (Suzuki and Hayashida, 2021)

Estrogen can enhance endothelium-dependent vasodilatation (Chan et al., 2001) or when estrogen level are low it
increase cardiovascular responses to stress (Altemus et al., 2001). Progesterone have a central thermogenic effect,
modulated at the level of the preoptic/anterior hypothalamus (Charkoudian and Johnson, 2000).

Evidence suggests that post-match sleep deprivation may result in depreciated cognitive functions in the following
morning, which may affect attention and decision-making skills during ensuing training sessions, potentially
resulting in an increased injury risk (Nédélec et al., 2015).
Exercise & Sports

● High estrogen levels (as in the preovulatory phase) enhances insulin sensitivity and action; while lower
estrogen levels and high progesterone levels (as in the mid-luteal phase) favours insulin resistance. Both
actions may result in very different glucose responses to the same meal or carbohydrate source.

● Estrogen facilitates fat oxidation during exercise, which may result in muscle glycogen ’sparing’ and thus
contribute to higher endurance performance. Although evidence is trivial, the above suggests that females
may be able to further ‘push’ in regards to endurance exercise during the luteal phase of the menstrual
cycle.
Exercise & Sports

Estrogen/E (vs Progesterone /P)

● Increases pain tolerance

● Increases ability to do endurance training because of its anabolic function and dependency on fat
substrate for fueling but when it comes to producing energy like in strength training, fat is not as efficient
as carbohydrates.

(in early follicular phase, estrogen is too low to show its good effects but best time is just before
ovulation when E is high but P is not risen up. P is catabolic in nature; to counteract the progesterone
induced catabolic activity, more protein is required before and after training.)

(Additionally, the variance in substrate oxidation between the luteal phase and follicular phase seems
intensity-dependent, and as exercise exceeds the lactate threshold the demand for increased carbohydrate
consumption outstrips the influence of estrogen. So, carbs loading should be done if indulging in the
endurance training, also know that carb loading is always to be done in before high intensity training)
● Unlike bone and muscle where estrogen improves function, in tendons and ligaments estrogen decreases
stiffness, and this directly affects performance and injury rates (making women more prone for
catastrophic ligament injury)
Exercise & Sports

During early follicular phase (day 1-5), low progesterone causes end of inflammatory response
increasing the risk for injury and picking up an illness. So better to optimise the nutrition and sleep,
and will quite likely to improve the cognitive function.
So basically days in follicular phase when estrogen starts to come up (when progesterone is still low),
we feel the best as estrogen is anabolic and neurostimulatory.
In late follicular phase(day 6-10), estrogen is higher and progesterone is still low, so feel energised,
decreased appetite and blood sugar. The muscles is in repair phase as estrogen is anabolic. Can focus
on endurance based training (as rising estrogen as seen in late follicular depends upon fat substrate)
and also on strength training but with carb loading.
Around ovulation (day 11-13), estrogen drops off initially but rises again i.e around 12 day, we will
get more gains from weightlifting i.e. resistance training but needs to be careful as estrogen messes
with collagen. This is good time for endu training we well.
Exercise & Sports

Just after ovulation (day 14-15), because of high progesterone, there is slightly high basal temperature due to
disturbed thermoregulation, which can lead to high HR, little breathing difficulty.
Luteal phase of the menstrual cycle is associated with higher core body temperature, greater cardiovascular strain
during submaximal steady-state exercise, and a heightened threshold for the onset of sweating. It may be important
to increase fluid intake during the luteal phase. Blood sugar may be unstable due to sugar cravings.
Mid luteal phase (day 16-20), body may feel lethargic and hungry due to progesterone but overall good time for
endurance training because of high estrogen (low P:E ratio) but make sure to eat more calories. There may be
cardiovascular strain so keep on monitoring the HR. Reaction time, neuromuscular coordination, and manual
dexterity diminishes when hormones are high. When hormones are high, plasma volume drops by approximately
8%, meaning that less is available for blood circulation and sweating. Improved endurance performance typically
occurs with high plasma volume, so hydration is particularly important during the luteal phase.
During late luteal phase (21-28 days), both hormones are lower again and body may feel like PMS and unstable
BS. Sleep may be affected causing problems with concentration and recovery. Exercise moderately. Body is better
to use fats instead of carbs which supports the aerobic workout. Eat more carbs, about .45 gram of carbs per pound
of bodyweight per hour (of training)
Exercise & Sports
Exercise & Sports
Exercise & Sports

Challenges to female athletes:

● Just before period, hormonal changes, including the sudden drop in levels of progesterone, affect the
body’s temperature control, which in turn can reduce the amount of 'REM' sleep. This is the stage of sleep
when most of our dreams occur. This all in trun affect an athelete and her performance
● Menstrual related symptoms are highly prevalent and highly individualised in female athletes.
● Almost all athletes perceived that menstrual symptoms impacted negatively on sporting performance.
● Support and treatment for menstrual symptoms varied for individuals, with athletes generally choosing to
adapt to or accept symptoms.
● Athletes’ comfort to discuss menstrual cycle concerns concerns/issues varied with many perceiving a
gender barrier in discussing menstrual cycle concerns/issues with male staff members.

Resultant Misconceptions and malpractices:

● I have to just be quite on top of [my symptoms], I think, if I’m training or competing
● athletes displayed an acceptance of their menstrual cycle symptoms or concerns, reporting that they do not
feel that menstrual cycle issues are acceptable reasons to take rest or abstain from training and they felt
that they must continue, regardless of pain or other symptoms
● Athletes managing their symptoms with drugs and OCP
Exercise & Sports

Reasons that were mentioned not to report absence of menstruation

Exercise & Sports Reasons that were mentioned not to report absence of menstruation
Exercise & Sports Reasons that were mentioned not to report absence of menstruation
Exercise & Sports

Factors that were mentioned to optimize care around menstrual problems in athletes
Exercise & Sports Factors that were mentioned to optimize care around menstrual problems in
athletes
Exercise & Sports Factors that were mentioned to optimize care around menstrual problems in
athletes
Exercise & Sports
Energy availability

Energy availability (EA) is the remaining dietary energy in the body after the energy expenditure from
physical activity has been considered; this remaining dietary energy is available to be utilized in the
body’s metabolic processes.

Previous data evaluating dietary intake and eating habits of female athletes reported that the majority of
athletes under consumed calories, in particular carbohydrates.

Failure to reach sufficient metabolic and caloric demands may elicit disruptions to menstruation,
performance, and bone mass, potentially increasing the risk for injury and osteoporosis

Obtaining optimal EA (40–45 kcal/kg FFM/day), eumenorrhea, and bone health are essential to
sustaining metabolism and maximizing performance in women

Lack of proper nutrition may lead to Relative Energy Deficiency in Sport (RED-S)/Female Athlete Triad
(Triad)

RED-S and the Triad both refer to disordered eating, or under consumption, and osteoporosis; the Triad
includes amenorrhea as an additional consideration for women

Amenorrhea is characterized by a lack of ovulation as a result of insufficient LH and FSH; both of which
would impact estrogen and progesterone concentrations.
Energy availability
Combined, the effects of RED-S or the Triad behaviors influence metabolic function, muscle protein
synthesis, bone health, immunity, and cardiovascular health; all of which may alter daily living and both
short- and long-term performance

Best practices to avoid RED-S or the Triad include adequate caloric intake to meet energy, metabolic, and
activity demands and sufficient intake of proper macronutrients.
Energy availability
Combined, the effects of RED-S or the Triad behaviors influence metabolic function, muscle protein
synthesis, bone health, immunity, and cardiovascular health; all of which may alter daily living and both
short- and long-term performance

Best practices to avoid RED-S or the Triad include adequate caloric intake to meet energy, metabolic, and
activity demands and sufficient intake of proper macronutrients.
Influence of ovarian hormones on GI motility

Ovarian hormones influence GI function because ovarian hormonal receptors have been found in the
gastric and small intestinal mucosa
GI transit duration tends to be prolonged during the luteal phase due to progesterone and fast at onset
of menses due to prostaglandin

Further support is given to the idea of a modulatory role of ovarian hormones on GI motility by the
frequent association between hormonal changes during pregnancy and the co-occurrence of GI
motility disorders. GI transit time is significantly prolonged in the third trimester when ovarian
hormone levels are increased. Although mechanical causes inherent to morphological changes during
pregnancy can account for bowel habit disturbances, it seems that the endocrinological changes are
more likely to be the accountable causes of GI motor impairments.
`
Day 1 – 5 or 7 – Period
Since progesterone is low at this time, the gut motility speeds up and can cause diarrhea (periods
poops)
Also increased levels of prostaglandins during this time making it more likely to experience diarrhea.
In medical conditions like IBS-D, period can significantly impact bowel function and quality of life
for a few days every month!

Day 6 or 8 – 13 or 14 – Follicular Phase

Estrogen is the predominant hormone. Usually, women will experience bowel movements that are
considered more or less “normal” at this time of the cycle.
Day 14 – Ovulation
Contrary to as early follicular phase, there is a rise in progesterone which will slow down gut motility
causing constipation for a few days or even until period
Constipation is a common symptom and can exacerbate conditions like IBS or endometriosis.
Not only does progesterone affect the movement of food, but it can also affect eating habits in the
days leading up to period. Progesterone has been linked to binge eating before and during
menstruation. Changes in the eating habits can affect stool odor, which may be why period poops can
smell worse than regular bowel movements.
Tips to help: Watch food habits around period. Avoid heavy, fatty foods that can cause constipation.
Try to incorporate more fiber and veggies into diet—especially if time-of-the-month tends to cause
constipation.
Day 15 – 28 – Luteal Phase

Typically, during the luteal phase and especially right before period, women can experience more gas, bloating,
water retention and changes to bowel movements due to the increase in progesterone. These symptoms start in
luteal phase and can persist until the first few days of period and beginning of a new cycle.

The types of food you eat can also affect bowel movements. For example, coffee has a laxative effect on many
people.

Progesterone may increase feelings of hunger and can cause cravings for foods high in fat or sugar, such as ice
cream or chocolate. The body has a hard time digesting these foods, and eating more of them can affect a person’s
bowel movements.
Day 15 – 28 – Luteal Phase

PMS-related changes in dietary habits may contribute to why some people notice differences in the
consistency, regularity, or smell of their stool before or during a period.

During luteal phase, body can’t utilize carbohydrates because of estrogen so recommend more
steady state exercise, skill work, and movement technique in these days leading up to period.

Add in Zinc, Magnesium, and Omega-3’s, and pre-track some high quality dark chocolate into
macros during the week leading up to period to help the inflammation and immunity
Day 15 – 28 – Luteal Phase

Research indicates that premenstrual compulsive eating has a physiological component.

According to a study published in the International Journal of Eating Disorders, ovarian hormones appear to play a major
role. The study showed that high progesterone levels during the premenstrual phase may lead to compulsive eating and
body dissatisfaction.

Estrogen, on the other hand, appears to be associated with a decrease in appetite. Estrogen is at its highest levels during
ovulation.

In a simplified sense, you’re likely to feel more dissatisfied about everything right before period. This dissatisfaction may
be a trigger for you to eat compulsively.

Premenstrual bingeing usually lasts a few days and ends once menstruation starts, although this isn’t always the case.

If compulsive eating continues outside of the menstrual cycle, adv to see doctor

Stress may also lead to emotional eating around period. Exercising, practicing relaxation techniques, getting regular sleep,
and maintaining a positive outlook can help manage stress.
The following tips may help people better manage period-related digestive disturbances:

● Eat plenty of natural fiber, including fruits, vegetables, and whole grains. High fiber foods help keep the
digestive system regular. Avoid compulsive eating by eating mindfully and smartfully.
● Do something physical. Moving around can help to relieve PMS-related bloating and discomfort and helps
keep the bowel moving.
● Try stool softeners. Stool softeners help stool to pass through the bowel more easily until hormone levels even
out.
● Take ibuprofen. Not only can ibuprofen help to reduce uterus cramping and discomfort, but it is also a
prostaglandin inhibitor. Sometimes, this effect may help to take the edge off period-related digestive
symptoms.
● Make healthy lifestyle choices

If period-related bowel disturbances get in the way of a person’s daily life, GO TO doctor about the best treatment
options.
Influence of ovarian hormones on GI disorder

Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both
healthy and IBS populations

Hormones can modulate pain processing by interacting with neuromodulator systems and the emotional
system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress,
which is a pivotal factor in IBS occurrence and symptom severity.

It is also noteworthy that many if not all the comorbid diseases associated with IBS also share this female
predominance. To name the most common, fibromyalgia, migraine, other functional GI disorders such as
functional dyspepsia, chronic pelvic pain, chronic fatigue syndrome, and depression all have sex ratio skewed
towards female gender

There is a strong correlation between IBS and dysmenorrhea and variations in ovarian hormone levels during the
menstrual cycle have been shown to modulate IBS symptomatology in women
Influence of ovarian hormones on GI disorder

Female IBS patients present higher activity of brain structures involved in emotional processing of pain
sensation (i.e., insula, cingulate cortex and amygdala) and greater connectivity between brain structures involved
in cortical control (i.e., prefrontal cortex).

IBS onset and symptoms severity are associated with acute or chronic stress; IBS female patients present
emotional hyper reactivity to stress (limbic system hyper reactivity to stress); levels of estradiol, progesterone
and stress hormones are positively correlated in rodent models of IBS

Recent findings suggest associations between immune activation and IBS, and especially, GI mucosal mast
cell infiltration is consistently reported in IBS patients; estrogens promote mast cell activation
Menstrual headaches/migraines

Migraine commonly affects adolescents, and menstrual migraine often begins in young girls. The
trigger thought to be partially responsible for menstrually associated migraine is a significant drop in
circulating estrogen that is noted during 2-3 days prior to onset of menses. If undiagnosed or
ineffectively treated, migraine can lead to disability, school absenteeism, emotional or social
difficulties, and chronification of headache. Thus, recognizing and accurately diagnosing migraine
and menstrual migraine, developing effective treatment strategies (both pharmacologic and
nonpharmacologic), and educating both the adolescent and her parents are important in order to
minimize the potential early disability of this disorder and limit the otherwise likely progression of
migraine to a disabling disorder of adulthood.

Characteristics of menstrual migraine, which include functional disability, increased headache severity,
and lack of aura, are often overlooked, and therefore menstrual migraine is often underdiagnosed. Use
of a 3-month diary to record migraine patterns can reveal the predictable patterns associated with
menstrual migraine, and a diary is demonstrated to be a useful tool in diagnosis.
Menstrual headaches/migraines
Diagnostic criteria for migraine without aura, excerpt from International Headache Society (IHS) classification of
headache

Migraine without aura (MO)

A. At least five attacks fulfilling B through D

B. Headache lasting 4–72 h (untreated or unsuccessfully treated)

C. Headache has at least two of the following characteristics:

1. Unilateral location

2. Pulsating quality

3. Moderate or severe intensity (inhibits or prohibits daily activities)

4. Aggravation by walking stairs or similar routine physical activity

D. During headache at least one of the following:

1. Nausea and/or vomiting

2. Photophobia and phonophobia

Menstrual headaches/migraines

Treatment alternatives for menstrual migraine include acute therapy and short- or long-term preventive
therapies. Acute therapy is given shortly after the migraine begins. Short-term preventive therapies are
effective when administered during the time that menstrual migraine is most likely to occur; the
treatment window is typically 2 days prior up to 3 days after the onset of menstruation.

If several attacks occur throughout the cycle, standard prophylactic agents should be used. Women with
exclusive 'menstrual' migraine may benefit from perimenstrual prophylaxis but this should only be
instigated once the association between migraine and menstruation has been confirmed with prospective
records kept for a minimum of three cycles.

NSAIDs are the treatment of choice in reducing migraine associated with menorrhagia and/or
dysmenorrhoea, otherwise perimenstrual oestrogen supplements using percutaneous or transdermal
oestrogens are recommended. Combined oral contraceptives are useful for women requiring
contraception although there is a tendency for attacks to occur during the pill-free interval. If these are
contraindicated, depot progestogen is an alternative as it also inhibits ovulation and can improve
migraine.
Liver abnormalities

The hormone levels are positively correlated to the severity of the liver disease. Treating
patients toward improved liver function resulted in regression of endocrine disturbance (Long
and Simmons, 1951). The liver is the primary site of estrogen metabolism. Any damage to
the liver impairs its capacity to metabolize and inactivate estrogens, resulting in increased
estrogen levels in the circulation.

https://www.facebook.com/healthspecificsacademy/photos/a.140063518434943/143087134
799248/
Exogenous ovarian hormones

The combination of estrogen and progesterone is used in two major treatment modalities: oral
contraceptives (OCP) and postmenopausal hormone replacement therapy (HRT)

The histopathologic appearance of the endometrium affected by OCP or HRT is influenced by many
factors.

After the prolonged use of OCP, an atrophic pattern of endometrium may develop. The hormonal
concentrations used to prevent conception are different from those used to treat menopausal
symptoms. A variety of histologic appearances ranging from secretory endometrium to hyperplasia
and even atrophy have been identified in patients receiving HRT.

In women receiving postmenopausal HRT, breast cancer risk for hormone receptor–positive cancers
and HER2-positive tumors increases. In women taking estrogen and progestin replacement for more
than 15 years, the risk of breast cancer increased by 83% compared with estrogen-only HRT, which
increased risk by 19%. Risks associated with HRT were found only in women with BMI less than
29.9 kg/m2, but not in women with a BMI more than 30 (HIGH VARIATION IN RESULTS OF
STUDIES)
Other drugs

Tamoxifen is a nonsteroidal antiestrogenic drug that is widely used as adjuvant chemotherapy in breast cancer
patients. The antiestrogenic effect of tamoxifen is attributed to its ability to compete with estrogen for binding
sites in tissues such as the breast; however, it also elicits a paradoxical estrogenic effect on the endometrium
that seems to be related to dose, duration of treatment, and menopausal status of the patient. Endometrial
biopsies from women taking tamoxifen are typically scanty, because tamoxifen induces fibrosis of the
endometrial stroma. The use of tamoxifen has been linked to an increased risk of developing endometrial
polyps, as well as adenomyosis, endometrial hyperplasia, endometrial carcinoma, and müllerian adenosarcoma.

Diet
Sleep

In women with stress induced, exercise induced, or functional hypothalamic hypogonadism, melatonin levels
are higher than normally present.

The relationship between melatonin and estrogen was also studied in breast cancer patients. High melatonin
levels decreased the amount of estrogen, and low melatonin caused an increase in estrogen

Melatonin is created in darkness and helps in facilitating the sleep. Late sleeper had higher estrogen which
increases risk for breast cancer.
Sleep

Around ovulation, we’re less tolerant of heat, because elevated progesterone delays sweat response, causing
body to take longer to expel excess warmth.
Just before period, hormonal changes, including the sudden drop in levels of progesterone, affect the body’s
temperature control, which in turn can reduce the amount of 'REM' sleep. This is the stage of sleep when most
of our dreams occur.
Changes in hormone levels also contribute to sleeping difficulties during pregnancy. Increased progesterone
levels can cause daytime sleepiness, particularly in the first trimester. High levels of oestrogen and
progesterone during pregnancy can also cause nasal swelling and lead to snoring.
During menopause, low levels of oestrogen may contribute to sleeping difficulties. Changes in hormone levels
mean that body temperature is less stable and there may be increases in adrenaline levels, both of which can
affect sleep. The loss of oestrogen causes body fat to move more to the stomach area, which increases the
chances of women having snoring and sleep apnoea.
Sleep

For women with severe premenstrual symptoms reduced levels of melatonin before bedtime just before their
menstrual period can cause poor sleep, including night-time awakenings or daytime sleepiness. Melatonin acts
on the ovaries directly through its antioxidant and anti-apoptotic properties, as well as its regulation of LH
mRNA in the ovaries (Tamura et al. 2009). The antigonadotropic effect was seen not only when melatonin
levels were too high, but also when melatonin levels were too low.

The capability of melatonin to act as a free radical scavenger is especially important because ovulation
stimulates a local inflammatory response, causing inflammatory cells such as macrophages and neutrophils to
produce free radicals such as ROS and RNS, which induce apoptosis in ovarian cells. Higher melatonin levels
in ovarian follicles offers the ovarian cells a greater chance of maturing and developing (Tamura et al. 2009).
Therefore, if a woman’s melatonin levels are too low, there may be an increase in the percentage of follicular
deaths which would result in a lower number of follicles that have the potential for ovulation.
Sleep

It appears that melatonin is beneficial in high concentrations when it is present in the ovaries because it
directly decreases apoptosis and acts as a free radical scavenger. Therefore, low melatonin levels in the ovaries
are detrimental to fertility.

On the other hand, high melatonin concentrations in the blood can inhibit ovulation by inhibiting the surge in
LH. It is necessary to determine the concentrations of The Effect of Melatonin on the Ovaries melatonin that
will be most beneficial in increasing ovulation by protecting and helping oocyte maturation, without being too
high to be antigonadotropic.
Sleep
Sleep

Sleep hygiene can also have a profound positive effect on sleep quality and ability to fall asleep. This includes
the following:
● Not drinking alcohol, coffee, or caffeine containing teas (in addition to other stimulates) four to six hours
before bed.
● Avoiding smoking before bedtime or during the night.
● Avoiding heavy meals and spicy/hot foods before going to bed.
● Increase the amount of daytime exercise but try avoiding exercise right before bed.
● Ensure your room is quiet, dark, not too hot, or too cold.
● Leave your room so that it is primarily associated with sleep (or sex), i.e. don’t turn your room into a
cinema or office, if possible.
● Try to have a consistent sleep routine.
● Restorative sleep requires a drop in core temperature but core temperature is slightly elevated during the
luteal phase due to progesterone. Sleep can be helped during this phase by ingesting cold tart cherry juice
an hour before bed. Not only does the cold aspect reduce core temperature, but the tart cherry juice
contains melatonin, a natural hormone that support body to reach its ‘deep sleep’ state.
● Several techniques like relaxation, yoga
● Consider medical condition like OSA, etc.
Mental health

Major depressive disorder (MDD) is associated with significant gender disparity. Women are afflicted with depression twice
more likely than men

Depressive disorders such as premenopausal dysphoric disorder and postpartum depression are gender-specific.

Interaction between various factors namely neurobiological, hormonal, genetic, social, environmental has been implicated to
explain these differences.

Structural differences between the brains of men and women, altered sensitivity to various neurotransmitters and hormones
like serotonin, gamma-aminobutyric acid (GABA), allopregnanolone, estrogen, and corticosteroids along with genetic
predisposition and cultural factors, such as lower health-seeking behaviors, social isolation, high incidence of abuse, and
marital and child-rearing stressors, contribute to the development of depression in women.

This increased susceptibility is seen only during reproductive years, especially during premenstrual, pregnancy, and
perimenopausal phase. The prevalence of depression in prepuberty and after the age of 55 years is almost equal between
males and females
Mental health

The burden of menstrual abnormalities caused by depression should not be

underestimated.

Interview Survey determined that 19% of women experienced menstrual

problems including menorrhagia, dysmenorrhea, and premenstrual syndrome
and they are twice more likely to suffer from depression and anxiety than those
without menstrual complaints.

Strong positive association is also seen between depression and early

menopause/perimenopause.

Depression can not only precede but can also hinder the treatment for
menorrhagia. Even the treatment of underlying depression can cause
menorrhagia.

Mechanism: It also revealed that depression and the number of menstrual

complaints were significantly correlated. This was explained by higher levels of
blood bradykinin and prostaglandin associated with stress, which causes
dilatation and increase in flow in pelvic blood vessels and hence causing
menorrhagia and pelvic pain

Mechanism: Both estrogen and progesterone (with its metabolite ALLO) are
known to have role in mental health. Low estrogen causes low serotonin. Low
progesterone ( ALLO) affects GABA and HPA axis
 6. MENSTRUAL SYNCING
Not to swagger, but cycling women know more than anyone how to handle ups and downs we're given. We've
been doing it on a monthly basis! We'll get through this, too
Which beverages can help support you during each week of your menstrual cycle? Here's what the research shows:

Week 1
Day 1 (first day of period) thru Day 7
Chamomile tea may ease period cramps by boosting glycine—an amino acid that calms uterine spasms. For extra pep, you can
turn to caffeine. But avoid drinking black tea within an hour of consuming iron in food or a supplement since it can block
absorption. For a caffeine-free energy-boost, sip peppermint tea. Stimulating compounds in peppermint (menthol & menthone)
activate brain areas that wake you up!

Week 2
Day 8 thru ovulation
Thanks to spiking estrogen, your energy is high—and if you want it even higher, drink caffeine. But if this hormonal energy boost
is too high for you, opt for chamomile tea since its naturally calming compounds help curb edginess. Spiking estrogen can make it
more difficult to concentrate by exciting your brain, but green tea can sharpen focus thanks to its combo of a small amount of
alertness-revving caffeine & calming amino acid l-theanine.

Week 3
8 days following ovulation
Rising progesterone & lower estrogen can sap your pep, but caffeine can bring it back up. Tip: Research shows taking small sips
of caff'd tea or coffee is better at revving alertness than drinking gulps because it curbs the build-up of fatiguing compounds in the
brain thru the day. Bonus: Caffeine is a mild diuretic that helps shed fluid you're retaining due to rising progesterone. Or you can
rev alertness with peppermint tea, which also nixes gas, another common side effect of elevated progesterone.

Week 4
Final 6 days
Cocoa, lemonade & other sugary drinks reduce premenstrual irritability by fueling the brain with glucose, giving it more energy to
control brain areas that manage emotions. Relaxing chamomile helps you sleep. And green tea revs energy—but without a large
amount of caffeine that can spur premenstrual irritability.
Which beverages can help support you during each week of your menstrual cycle? Here's what the research shows:

SOURCES:
Yulan Wang, et al., "A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.)
ingestion," Journal of Agricultural and Food Chemistry, 53 (2005): 191-196
Mark Moss, et al, "Modulation of cognitive performance and mood by aromas of peppermint and ylang-ylang," The International
Journal of Neuroscience, 118 (2008): 59-77
Anna C Nobre, Anling Rao, Gail N Owen, "L-theanine, a natural constituent in tea, and its effect on mental state," Asia Pacific
Journal of Clinical Nutrition, 17 (2008): 167-168
James K. Wyatt, et al., "Low-dose repeated caffeine administration for circadian-phase-dependent performance degradation
during extended wakefulness," Sleep, 27 (2004): 374-381
C. Nathan DeWall, et al., "Sweetened blood cools hot tempers: physiological self‐control and aggression," Aggressive Behavior,
November 9, 2010
Ovulation signs
For complete info-

https://sprintmedical.in/blog/o
vulation-pain-causes-and-
symptoms-of-ovulation-
cramping

https://www.shecares.com/pr
egnancy/ovulation/ovulation-
signs-symptoms

Read both the blogs. May

come in the test.
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