MENSTRUATION-RELATED DISORDERS

Amenorrhea
Heavy Menstrual Bleeding
Dysmenorrhea
Abnormal Uterine Bleeding with Ovulatory Dysfunction
Premenstrual Syndrome and Premenstrual Dysphoric Disorder

WRITTEN REPORT

Group number 4:

Arancon, Yentl Madisson

Devibar, Kesia

Kho, Joan Mary

Panerio, Janesel
 AMENORRHEA

Introduction

Amenorrhea is the absence of menstruation, often defined as missing one or more menstrual
periods. It is defined as no menstrual bleeding in a 90-day period and can be either primary or secondary
in nature. Amenorrhea is a normal feature in prepubertal, pregnant, and postmenopausal females. In
females of reproductive age, diagnosing amenorrhea is a matter of first determining whether pregnancy
is the etiology. In the absence of pregnancy, the challenge is to determine the exact cause of absent
menses.

Primary amenorrhea is the absence of menses by age 15 years in women who have never
menstruated. Secondary amenorrhea is the absence of menses for three cycles or for 6 months in a
previously menstruating woman. Primary amenorrhea occurs in less than 0.1% of the general population.
Secondary amenorrhea, in comparison, has an incidence of 3% to 4% in the general population and
occurs more frequently in women younger than 25 years with a history of menstrual irregularities and in
those involved in competitive athletics.

Etiology

In two-thirds of women, menses occur generally at 28 + 3 days, and cycle lengths of 18 to 40

days are considered within the normal range. Amenorrhea is not itself a diagnosis, but a sign of a
disorder. There are three broad categories of amenorrhea etiology:

 Anatomical causes, including pregnancy and uterine structural abnormalities

 Endocrine disturbances leading to chronic anovulation
 Ovarian insufficiency/failure

While a urine pregnancy test should be one of the first steps in evaluating amenorrhea, the
majority of primary amenorrhea cases can be attributed to either anomalies involving (i) the
hypothalamic–pituitary axis resulting in endocrine disturbances, (ii) ovarian function or (iii)
outflow tract. Similarly, greater than 50% of secondary amenorrhea cases are due to the impact of
disturbances of the hypothalamic–pituitary–adrenal (HPA) axis or the hypothalamic–
pituitary-ovarian (HPO) axis. Therefore, in organizing an approach to diagnosis and treatment, it is
helpful to consider the organ systems involved in the menstrual cycle, which include the uterus, ovaries,
anterior pituitary, and hypothalamus.

Pathophysiology

Ovulation is required for the follicle (an estrogen-secreting body) to become a corpus luteum (a
progesterone-secreting body). Without ovulation, the proper sequence of estrogen production,
progesterone production, and estrogen/progesterone withdrawal will not occur. This can result in
amenorrhea. Anovulation can occur secondary to endocrine disturbances or ovarian insufficiency. Each
organ in the HPO axis, along with the uterus, is of importance in determining amenorrhea’s etiology and
pathophysiology. Beginning with the uterus/outflow tract and progressing caudally will result in a
comprehensive differential diagnosis. However, coexisting physical signs and symptoms, and a thorough
history, typically help the clinician prioritize evaluation steps.
Uterus/Outflow Tract

For menstruation to occur, a uterus, functional endometrium, and patent vagina must be present.
Several anatomic abnormalities may cause amenorrhea. Congenital anomalies such as imperforate hymen
or uterine agenesis may be discovered by physical examination. An acquired condition of the genital
tract, such as Asherman’s syndrome or cervical stenosis, is more likely in secondary amenorrhea.

Ovaries

Normal ovarian function is critical for menstruation to occur. The ovaries must respond
appropriately to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by secreting estrogen
and progesterone in the proper sequence toinfluence endometrial growth and shedding. Primary ovarian
insufficiency occurs when potentially viable primordial follicles in the ovaries have been depleted.

Estrogen production from the remaining ovarian follicles is insufficient to stimulate endometrial
growth in the absence of follicles. The etiologies for primary ovarian insufficiency include bilateral
oophorectomy, genetic anomalies, autoimmunity and iatrogenic causes as a result of radiation or
chemotherapy. However, in 90% of cases, the cause cannot be identified.

Hormonal fluctuations with the normal menstrual cycle. (FSH, follicle-stimulating hormone; LH, luteinizing
hormone.)

Clinical Presentation

 General
 Although patients may be concerned about the cessation of menses and implications for
fertility, patients are generally not in acute physical distress.
 Symptoms
 Patients will note cessation of menses.
 Patients may complain of infertility, vaginal dryness, or decreased libido.
 Signs
 Cessation of menses for more than 6 months in women with establishedmenstruation,
absence of menses by age 16 in the presence of normalsecondary sexual development,
or absence of menses by age 14 in theabsence of normal secondary sexual development.
 Recent significant weight loss or weight gain.
  Presence of acne, hirsutism, hair loss, or acanthosis nigricans maysuggest androgen
excess.
 Laboratory Tests
 Pregnancy test
 Serum FSH and LH
 Thyroid-stimulating hormone
 Prolactin
 If hyperandrogenic state (eg, PCOS) is suspected, consider free and total estosterone,
dehydroepiandrosterone, fasting glucose, and fasting lipid panel
 Other Diagnostic Tests
 Progesterone challenge to confirm functional anatomy and adequate estrogenization.
 Pelvic ultrasound to evaluate for polycystic ovaries, presence/absence of uterus, and/or
structural abnormalities of the reproductive tract organs.

Desired Outcomes

In general, the treatment options for amenorrhea depend on its causes. Therapeutic modalities
for amenorrhea should ensure the occurrence of normal puberty and restore the menstrual cycle.
Treatment goals include bone density preservation, bone loss prevention, and ovulation restoration to
improve fertility if desired. Hypoestrogenism may affect quality of life via hot flash induction (premature
ovarian failure), dyspareunia, and, in prepubertal females, lack of secondary sexual characteristics and
absence of menarche. Treatment is targetedat reversing these effects.

Treatment

 Pharmacologic Treatment
For hypoestrogenic conditions associated with primary or secondary amenorrhea,
historically estrogen has been supplemented as an oral contraceptive, conjugated equine
estrogen, or estradiol patch, in conjunction with progestin in an attempt to decrease osteoporosis
risk. However, data supporting estrogen supplementation in FHA are based on a limited number
of studies with small sample size and short follow-ups. Therefore, the primary approach for FHA
should be the correction of energy balance to restore HPO axis function. The 2017 Endocrine
Society Clinical Practice Guideline for FHA recommends the short-term use of transdermal
estradiol with cyclic oral progestins, after an adequate trial of nonpharmacological therapy (eg,
psychological and nutritional intervention). Combined hormonal contraceptives (CHC) and
synthetic ethinyl estradiol are no longer recommended as first-line agents for patients with FHA.
 Non-pharmacologic Treatment
Non-pharmacologic therapy for amenorrhea varies depending upon the underlying cause.
Amenorrhea secondary to anorexia may respond to weight gain. In young women for whom
excessive exercise is an underlying cause, reduction of exercise quantity and intensity are
important. Cognitive behavioral therapy has been shown to restore- ovarian function in women
with FHA. In 2017, the Endocrine Society Clinical Practice Guideline recommended a reasonable
trial of psychological, nutrition and/or modified exercise intervention prior to use of
pharmacotherapy in patients with FHA. In medication-induced hyperprolactinemia, the clinician
may consider alternative agents that do not inhibit dopamine receptors or increase prolactin
levels.

Medications That May Induce Hyperprolactinemia

Evaluation of Therapeutic Outcomes
Conclusion

Primary amenorrhea due to chromosomal aberration is an uncommon condition requiring an early

and accurate diagnosis. Turner's syndrome is a relatively common cause of this condition. Management
should be multidisciplinary and individualized according to the patient's age and symptom at
presentation. Thus it is concluded that amenorrhea is a menstrual associated problem affecting women
all over the world. Therefore it is important to identify those factors responsible for causing
primary/secondary amenorrhea in adolescent girls and women for the sake of their healthy reproductive
functioning.
Case Study:

A 37-year-old woman presents to your office for her annual visit. For the past 5 years she has
noted irregular menses, but now she has not had a period in 7 months and wonders if this is abnormal.

1. How is amenorrhea defined?

Primary amenorrhea is the absence of menstruation by age 16. This patient is considered to have
secondary amenorrhea – defined as cessation of an established menstruation for 3 months in a
woman with a history of regular cycles, but now without menses.

2. How should this patient be evaluated?

The initial priority is to make sure that she is not pregnant. Once that has been ruled out, a
detailed history of reproductive events leading up to the occurrence of amenorrhea is obtained.
General questions about health and lifestyle may identify a history of systemic illness or any pattern
of excessive stress (physical, psychological, or nutritional) that could affect hypothalamic function. A
history of past and/or present use of medication – particularly oral contraceptives or other types of
hormonal contraception (Depo-Provera) – can be very illuminating.

The patient’s overall body habitus, height, and weight should be determined. This may reveal
very low body weight (decreased percentage of body fat) associated with hypothalamic amenorrhea,
or upper body segment obesity (truncal obesity), often associated with insulin resistance and
hyperandrogenism. The presence of hirsutism would indicate the possibility of polycystic ovarian
syndrome (PCOS), or less likely an adrenal or ovarian androgen-producing tumor if progression is
rapid or associated with virilization. A rapid pulse may suggest hyperthyroidism, whereas a slow pulse
may indicate the possibility of hypothyroidism. Signs of Graves disease, such as exophthalmos, lid
retraction, or tremor would suggest thyroid dysfunction, as would a palpable goiter or other nodule.

Initially, the simplest panel would be FSH (follicle-stimulating hormone), TSH (thyroid-stimulating
hormone), and prolactin.

3. Her TSH and prolactin are both normal. The FSH level is not in the menopausal range. What is the
next step?

This patient does not have evidence for thyroid dysfunction or prolactinoma. She has a normal
reproductive tract and either too much unopposed estrogen or not enough. Administration of
progestin for a week to induce withdrawal bleeding could be the next step. If she does not have
bleeding, then an estrogen/progesterone challenge would be helpful in differentiating between a
structural problem (eg, Asherman syndrome) and hypogonadotropic hypogonadism (eg, Sheehan
syndrome). A “positive” withdrawal bleed after progestin therapy would suggest PCOS or some type
of hypothalamic dysfunction. She appears to have eugonadotropic hypogonadism – most likely to be
PCOS. However, to make a more definitive diagnosis, a panel of testosterone, DHEA
(dehydroepiandrosterone), and 17-hydroxyprogesterone would be helpful.

4. She has a “period” after 7 days of progestin therapy and her examination suggests PCOS. As she is
not attempting to get pregnant, what is the best medical therapy to treat anovulation and
amenorrhea?
 Oral contraceptives are very effective agents in the long-term management of PCOS. They break
the cycle through suppression of pituitary LH (luteinizing hormone) secretion, suppression of ovarian
androgen secretion, and increased production of circulating sex hormone-binding globulin (SHBG).
Oral contraceptives are also associated with a reduction in the risk of endometrial cancer.
Alternatively, cyclic progestin therapy is an option. Metformin and other insulin-sensitizing agents
have been explored, but are currently unproven therapeutic options.

5. Does weight loss improve ovarian function in obese women with PCOS?

Yes – obesity contributes substantially to reproductive and metabolic abnormalities in women

with PCOS. Weight loss can improve the fundamental aspects of the endocrine syndrome by
decreasing circulating androgen levels and causing spontaneous resumption of menses. Other
benefits include decreased circulating testosterone levels largely mediated through increases in
SHBG. In addition, weight loss can result in significant improvement in the risk of diabetes and
cardiovascular disease. Lifestyle modification (diet and exercise) should be promoted as the main
primary treatment for all obese women with PCOS.