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Amenorrhoea

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Description: Amenorrhoea is the absence of menstrual periods in a woman of reproductive age.
Type: Amenorrhea itself is a symptom rather than a single disease and can result from various underlying conditions. Some causes include hormonal imbalances, structural problems, and genetic disorders. One of the genetic conditions that can cause amenorrhea is Turner syndrome, which involves the partial or complete absence of one of the X chromosomes (monosomy X). Turner syndrome is not typically inherited but occurs as a random genetic event.

Another genetic cause can be Androgen Insensitivity Syndrome (AIS), which is X-linked recessive. In AIS, individuals who are genetically male (with one X and one Y chromosome) have a partial or complete inability to respond to androgens, leading to the development of female physical characteristics and often primary amenorrhea.

In summary, amenorrhea can have various genetic transmission types depending on the underlying condition, including monosomy X in Turner syndrome (random event) and X-linked recessive in Androgen Insensitivity Syndrome.
Signs And Symptoms: Amenorrhea is the absence of menstruation. Here are its signs and symptoms:

1. **Primary Amenorrhea**:
- Failure to begin menstruation by age 15 or within five years of breast development.

2. **Secondary Amenorrhea**:
- Absence of menstrual periods for three consecutive cycles or more than six months in women who previously had regular menstruation.

Other symptoms that may accompany amenorrhea, depending on the underlying cause, include:
- Milky nipple discharge
- Hair loss
- Headache
- Vision changes
- Excess facial hair
- Pelvic pain
- Acne
Prognosis: The prognosis for amenorrhea largely depends on the underlying cause. For primary amenorrhea (when menstrual periods have not started by age 15), prognosis can vary depending on whether the cause is related to hormonal imbalances, genetic conditions, or anatomical abnormalities. Early diagnosis and treatment are crucial for a better outcome.

For secondary amenorrhea (when menstrual periods stop for three months or more in a woman who previously had regular cycles), the prognosis is generally good if the underlying cause, such as stress, significant weight loss, or polycystic ovary syndrome (PCOS), is identified and managed effectively. Treatment may involve lifestyle changes, medication, or hormonal therapy, depending on the cause.

In many cases, menstrual cycles can be resumed with appropriate intervention. However, the prognosis can vary widely from person to person. Regular follow-ups with a healthcare provider are important for ongoing management and monitoring.
Onset: Amenorrhoea is the absence of menstruation. It can be classified based on onset:

1. **Primary Amenorrhoea**: This occurs when a girl has not begun menstruating by age 15 or within five years of the onset of puberty.
2. **Secondary Amenorrhoea**: This occurs when a woman who previously had regular periods stops menstruating for three consecutive cycles or for more than six months.

The possible causes can include hormonal imbalances, genetic factors, anatomical abnormalities, and lifestyle factors such as stress and excessive exercise. Treatment options depend on the underlying cause.
Prevalence: The prevalence of amenorrhea varies based on the population and type (primary or secondary). Primary amenorrhea, the absence of menstruation by age 15 in girls who have not developed secondary sexual characteristics or by age 16 in girls who have developed secondary sexual characteristics, has a prevalence of less than 0.1%. Secondary amenorrhea, the absence of menstruation for three cycles or six months in women who previously had regular menstruation, affects about 3-5% of women of reproductive age.
Epidemiology: Amenorrhea is the absence of menstrual periods. Here's an overview of its epidemiology:

### Epidemiology

1. **Prevalence:** Amenorrhea can affect women at various stages of life. Primary amenorrhea (when menstruation has not started by age 15) is less common, affecting less than 0.1% of adolescent girls. Secondary amenorrhea (when menstruation stops for more than three cycles or six months in women who previously had periods) is more prevalent, affecting up to 5% of reproductive-age women.

2. **Age and Onset:** Primary amenorrhea is usually identified in adolescence. Secondary amenorrhea can occur at any reproductive age but is often noted in women in their 20s and 30s.

3. **Risk Factors:** Factors contributing to amenorrhea include:
- **Genetics:** Family history of menstrual irregularities.
- **Health Conditions:** Polycystic ovary syndrome (PCOS), thyroid disorders, pituitary tumors, and chronic conditions.
- **Lifestyle Factors:** Extreme weight loss, excessive exercise, and stress.
- **Medications:** Contraceptives, antipsychotics, antidepressants, and chemotherapy drugs.

4. **Associated Conditions:** Amenorrhea can be associated with conditions like infertility, osteoporosis (due to prolonged low estrogen), and cardiovascular issues.

Understanding these epidemiological factors aids in the identification, prevention, and management of amenorrhea in various populations.
Intractability: Amenorrhoea, which is the absence of menstrual periods, is not inherently intractable. The condition can often be managed or resolved depending on its underlying cause. Potential causes include hormonal imbalances, polycystic ovary syndrome (PCOS), thyroid disorders, excessive exercise, stress, and certain medications. Treatment varies and may involve lifestyle changes, medication to address hormonal issues, or treating the underlying health condition. A thorough evaluation by a healthcare provider is essential to determine the appropriate intervention.
Disease Severity: Amenorrhoea is not a disease but a symptom characterized by the absence of menstrual periods. It can vary in severity depending on the underlying cause. It can be classified into primary and secondary amenorrhoea. Primary amenorrhoea involves a failure to start menstruating by the age of 15. Secondary amenorrhoea refers to the cessation of menstruation in someone who previously had normal periods.

The severity and treatment depend on factors such as hormonal imbalances, lifestyle factors, underlying medical conditions, and structural abnormalities. It is important to identify and treat the underlying cause to manage amenorrhoea effectively.
Healthcare Professionals: Disease Ontology ID - DOID:13938
Pathophysiology: Although amenorrhea has multiple potential causes, ultimately, it is the result of hormonal imbalance or an anatomical abnormality.Physiologically, menstruation is controlled by the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH acts on the pituitary to stimulate the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH then act on the ovaries to stimulate the production of estrogen and progesterone which, respectively, control the proliferative and secretary phases of the menstrual cycle. Prolactin also influences the menstrual cycle as it suppresses the release of LH and FSH from the pituitary. Similarly, thyroid hormone also affects the menstrual cycle. Low levels of thyroid hormone stimulate the release of TRH from the hypothalamus, which in turn increases both TSH and prolactin release. This increase in prolactin suppresses the release of LH and FSH through a negative feedback mechanism. Amenorrhea can be caused by any mechanism that disrupts this hypothalamic-pituitary-ovarian axis, whether that it be by hormonal imbalance or by disruption of feedback mechanisms.
Carrier Status: Amenorrhea refers to the absence of menstruation. It is not a condition with a carrier status, as it is not an inheritable disease caused by a single gene mutation. Instead, amenorrhea can result from various factors, including hormonal imbalances, lifestyle factors, reproductive organ issues, or certain medical conditions. "Nan" typically stands for "not a number" and is not relevant to the context of amenorrhea.
Mechanism: Amenorrhea refers to the absence of menstruation. It can be classified into two types: primary amenorrhea, where menstruation has not begun by age 15, and secondary amenorrhea, where menstruation starts but then stops for three or more consecutive months in a woman with previously regular cycles.

### Mechanism
Amenorrhea can result from various factors affecting the hypothalamic-pituitary-ovarian (HPO) axis, uterine structure, or endocrine function. Here's a breakdown:

1. **Hypothalamic Causes**:
- Stress, excessive exercise, or significant weight loss can inhibit the release of gonadotropin-releasing hormone (GnRH).
- Conditions such as functional hypothalamic amenorrhea (FHA) disrupt the HPO axis.

2. **Pituitary Causes**:
- Pituitary tumors (e.g., prolactinomas) can alter hormone production.
- Hyperprolactinemia inhibits GnRH secretion, affecting the menstrual cycle.

3. **Ovarian Causes**:
- Polycystic ovary syndrome (PCOS) is a common cause where hormonal imbalances disrupt ovulation.
- Premature ovarian insufficiency (POI) where there's an early depletion of ovarian follicles.

4. **Uterine Causes**:
- Asherman's Syndrome, involving intrauterine adhesions, can physically prevent menstruation.

5. **Endocrine Causes**:
- Thyroid disorders (both hypothyroidism and hyperthyroidism).
- Adrenal disorders affecting steroid hormone synthesis.

### Molecular Mechanisms
At a molecular level, amenorrhea involves several pathways and hormonal interactions:

1. **GnRH Regulation**:
- Kisspeptins, neuropeptides involved in the regulation of GnRH, play a vital role. Mutations or disruptions in the kisspeptin receptor (KISS1R) can lead to amenorrhea.
- Leptin, a hormone produced by adipose tissue, influences GnRH release. Low levels, often due to low body fat, can suppress GnRH secretion.

2. **FSH and LH Secretion**:
- GnRH stimulates the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- Disruptions in GnRH lead to altered FSH and LH levels, affecting follicular maturation and ovulation.

3. **Ovarian Hormones**:
- FSH and LH regulate estrogen and progesterone production by the ovaries.
- In PCOS, insulin resistance can lead to hyperandrogenism, disturbing normal ovarian function and leading to amenorrhea.

4. **Prolactin Regulation**:
- Hyperprolactinemia from pituitary adenomas can inhibit GnRH secretion through dopaminergic pathways, affecting the menstrual cycle.

5. **Insulin and Androgens**:
- In PCOS, hyperinsulinemia leads to increased ovarian androgen production.
- Elevated androgens disrupt follicular development and ovulation, contributing to amenorrhea.

6. **Genetic Factors**:
- Mutations in genes regulating hormone receptors or signaling pathways (e.g., FSHR, LHR) can cause amenorrhea.
- Genetic syndromes like Turner syndrome (45,XO) affect ovarian development and function.

Understanding these mechanisms aids in diagnosing and treating amenorrhea based on its underlying cause.
Treatment: Treatment for amenorrhea varies based on the underlying condition. Treatment not only focuses on restoring menstruation, if possible, but also preventing additional complications associated with the underlying cause of amenorrhea.
Compassionate Use Treatment: Amenorrhea, the absence of menstruation, may sometimes require treatments that fall under compassionate use, off-label, or experimental categories, particularly in complex cases where standard treatments fail. These include:

1. **Hormonal Treatments:** While many hormonal therapies are standard, some may be used off-label depending on the underlying cause of amenorrhea. Examples include certain formulations of estrogen, progesterone, or combined oral contraceptives that aren't specifically approved for amenorrhea but can be effective.

2. **GnRH Analogues:** These are often used off-label to manage amenorrhea associated with conditions like endometriosis or polycystic ovary syndrome (PCOS).

3. **Metformin:** Often approved for diabetes, metformin is used off-label to restore menstrual cycles in women with PCOS.

4. **Clomiphene Citrate:** Although primarily used for infertility, clomiphene can be prescribed off-label to induce ovulation and menstrual cycles in women with certain types of amenorrhea.

5. **Osteoporosis Medications:** In cases of amenorrhea leading to significant bone density loss, treatments like bisphosphonates or selective estrogen receptor modulators (SERMs) might be used compassionately.

In all cases, close supervision by a healthcare provider is essential to tailor treatments to the individual's specific needs and monitor for potential side effects.
Lifestyle Recommendations: Lifestyle recommendations for managing amenorrhea (absence of menstrual periods) often focus on addressing potential underlying causes and improving overall health. Here are some general suggestions:

1. **Maintain a Healthy Weight**: Both underweight and overweight can affect menstrual cycles. Aim for a balanced diet rich in nutrients.

2. **Regular Exercise**: Moderate exercise can help regulate periods, but excessive physical activity may cause or exacerbate amenorrhea. Strive for balance.

3. **Stress Management**: High stress levels can impact hormonal balance. Techniques such as yoga, meditation, and relaxation exercises can be beneficial.

4. **Avoid Smoking and Limit Alcohol**: These can negatively affect menstrual health.

5. **Healthy Eating Habits**: Focus on a balanced diet with adequate calories and nutrients to support hormonal balance.

6. **Adequate Sleep**: Good sleep hygiene can help regulate hormones and overall health.

If lifestyle modifications aren't effective in resolving amenorrhea, it's important to seek medical advice for further evaluation and treatment options.
Medication: For amenorrhoea, it's essential to identify the underlying cause to determine appropriate treatment. Common medications prescribed for amenorrhoea include:

1. **Hormonal Treatments:**
- **Oral Contraceptive Pills:** Used to regulate menstrual cycles.
- **Progesterone:** Helps induce menstrual periods in women who have not menstruated for a long while.
- **Estrogen Replacement Therapy:** Recommended for women with estrogen deficiency.

2. **Dopamine Agonists:**
- For women with hyperprolactinemia (elevated levels of prolactin), medications such as **bromocriptine** or **cabergoline** might be prescribed to reduce prolactin levels.

3. **Thyroid Hormone Replacement:**
- For those with hypothyroidism, **levothyroxine** can be used to restore hormone balance.

4. **Metformin:**
- Often used for women with polycystic ovary syndrome (PCOS) to help regulate menstrual cycles and improve insulin sensitivity.

Consultation with a healthcare provider is essential to determine the appropriate medication based on the specific cause of amenorrhoea.
Repurposable Drugs: Repurposable drugs for amenorrhea (the absence of menstruation) include:

1. **Metformin**: Commonly used for type 2 diabetes, it is particularly effective in women with polycystic ovary syndrome (PCOS) to help restore regular menstrual cycles.
2. **Clomiphene citrate (Clomid)**: Originally used for ovulation induction, it can be used in women with PCOS or other ovulatory disorders to stimulate menstruation.
3. **Letrozole (Femara)**: An aromatase inhibitor primarily used for breast cancer treatment; it can also be used off-label to induce ovulation in cases of amenorrhea related to PCOS.
4. **Hormone Replacement Therapy (HRT)**: Typically used for menopausal symptoms, it can be employed to induce menstruation in women experiencing amenorrhea due to hormonal imbalances.

Always consult a healthcare provider for personalized treatment options.
Metabolites: Amenorrhea is the absence of menstruation. When investigating amenorrhea, certain metabolites can provide crucial insights into underlying causes. Metabolites of interest may include:

1. **Hormone Metabolites**:
- **Estradiol (E2)**: Lower levels might indicate ovarian insufficiency.
- **Progesterone**: Low levels can be indicative of anovulation.
- **Luteinizing Hormone (LH)** and **Follicle-Stimulating Hormone (FSH)**: Their levels help differentiate between primary ovarian insufficiency (high levels) and hypothalamic or pituitary causes (low levels).
- **Testosterone**: Elevated in conditions like polycystic ovary syndrome (PCOS).

2. **Glucose and Insulin Metabolites**:
- Elevated glucose and insulin levels might hint at insulin resistance, commonly associated with PCOS.

3. **Lipid Profile**:
- Abnormalities in lipid metabolism can correlate with endocrine disorders that might cause amenorrhea, like PCOS.

These metabolites can be detected through blood tests and used to determine the underlying cause of amenorrhea, guiding appropriate treatment.
Nutraceuticals: Nutraceuticals for amenorrhea might include:

1. **Vitex agnus-castus (Chasteberry)**: This herbal supplement is thought to help normalize hormone levels.
2. **Vitamin D**: Deficiencies in Vitamin D have been linked to menstrual irregularities, including amenorrhea.
3. **Omega-3 fatty acids**: These are found in fish oil supplements and may support overall hormonal balance.
4. **Myo-inositol**: This supplement can improve insulin resistance and support ovarian function, particularly in cases of polycystic ovary syndrome (PCOS)-related amenorrhea.
5. **Vitamin B6**: Helps in the regulation of hormones and might alleviate symptoms of amenorrhea.
6. **Magnesium**: Important for hormone regulation and may help reduce menstrual irregularities.

Always consult with a healthcare professional before starting any new supplement regimen.
Peptides: Amenorrhea, the absence of menstruation, does not have direct treatment strategies involving peptides or nanotechnology (nan). The approach to managing amenorrhea typically depends on its underlying cause, which may involve hormonal therapies, lifestyle changes, or addressing any specific health conditions. Peptides and nanotechnology are areas of ongoing research, but they are not standard treatments for amenorrhea as of now.