Day 1

Menopause
• occurs around 45-55 years, when the ovaries stop ovulating and menstrual periods end
• Most women experience several years of changes in their menstrual periods before stopping completely
◦ Menstrual periods more or less often than usual
◦ Have bleeding that lasts for fewer days
◦ Skip one or more menstrual periods

Symptoms
◦ As ovaries stop working, estrogen levels fall, leading to many symptoms – these often begin during menopausal transition, before stopping periods completely
◦ Hot flashes is the most common, affecting 60-80% of women
◦ Typically begin as a sudden feeling of heat in the upper chest and face – and spreads throughout the body lasting 2 to 4 mins
◦ Some sweat and then have chills and others have a feeling of anxiety or heart palpitations
◦ These can occur once or twice a day, or as often as once per hour
◦ Most women will continue to have hot flashes for about 4 years (on average)
◦ Hot flashes are more common at night which as called night sweats
◦ As a result of interrupted sleep, women may develop other problems such as fatigue, irritability, difficulty concentrating and mood swings
◦ During the transition to menopause some women have problems falling asleep or stay asleep – sleeping aids may help
◦ As levels of estrogen decreases – tissues inside the vagina and urethra can become thin and dry – cause discomfort, itching or pain
◦ Depression – Some women may develop new problems with mood – sadness, difficulty concentrating, feeling uninterested in normal activities and sleeping too much or having difficulty sleeping

Treatment
◦ Not all women require treatment for menopause symptoms. For mild:
◦ Hot flashes and night sweats:
‣ Dress in layers so you can take clothes off when too hot
‣ Keep thermostat down and avoid hot drinks
‣ Put a cold, wet washcloth against neck during flashes
‣ Smoking cessation (smoking makes it worse)
◦ Vaginal dryness
‣ Lubricants before sexual intercourse
‣ Vaginal moisturizer such as Replens or Lubrin
◦ Sleep problems
‣ Sleep and wake up at the same time everyday
‣ Avoid caffeine in the afternoon and limit alcohol
◦ Depression
‣ Stay active and exercise
‣ Seek social support
• For more severe symptoms:
◦ Hormone therapy – estrogen is the most effective treatment for hot flashes
‣ It is safe, low risk and effective for healthy women
‣ It should be started before the age of 60 and is given for up to 5 years
‣ It is not recommended for women with a history of or high risk for breast cancer, heart disease and stroke
‣ Involves a combination of estrogen and progestin (women with hysterectomy only need estrogen)
‣ Comes in pill taken by mouth, skin patch, vaginal ring, skin gel/cream/spray
‣ Hormone therapy may help with vaginal dryness, depression and other mood problems
‣ Some may need antidepressant medications
‣ Vaginal estrogen can help with vaginal dryness – it comes in a lower dose and not taken with progestin – comes in a cream, tablet, or flexible plastic ring
◦ Non estrogen treatments
‣ For controlling hot flashes – Paroxetine – used for depression but can be taken at lower dose to treat hot flashes
‣ Gabapentin – single bedtime dose or during the day
‣ Antidepressants- Venlafaxine, citalopram
‣ Stress management, relaxation

Sources:
UpToDate

Uterine fibroids
• Microscopic or very large tumors that grow in the uterus and are usually benign
• They can grow in the myometrium, under the surface of the uterine lining (submucosal), or under the outside lining of the uterus (subserosal), or be pedunculated

Causes
◦ Uterine fibroids are common – 1 in 5 women may have them during their childbearing years – half of all women have fibroids by 50
◦ Rare in women under age 20 and more common in African American women
◦ They are thought to be caused by hormones or can be genetic
◦ The prevalence of significant fibroids peaks in perimenopausal years and declines after menopause
• Several factors may affect a women’s risk for having uterine fibroids including:
◦ Older age
◦ African American race
◦ Obesity
◦ Family history
◦ Hypertension
◦ No history of pregnancy
◦ Vitamin D deficiency
◦ Food additive consumption
◦ Use of soybean milk
• Factors that may lower the risk of fibroids
◦ Pregnancy
◦ Long term use of oral or injectable contraceptives

Clinical presentation
◦ Menstrual disturbances including menorrhagia, dysmenorrhea and intermenstrual bleeding
◦ Pelvic pain
◦ Sensations of bloating, increased urinary frequency and bowel disturbance
◦ Fibroids may compromise reproduction function:
‣ Subfertility, early pregnancy loss and later pregnancy complications such as pain, preterm labor, increased need for Caesarean section and postpartum hemorrhage
◦ Large fibroids may distend the abdomen
◦ Abnormal bleeding occurs in 30% of symptomatic women
◦ Bloating and pelvic discomfort

Diagnosis
◦ Sometimes are found in asymptomatic women during routine pelvic exam or incidentally on imaging
◦ Ultrasound is the preferred imaging modality
◦ Transvaginal ultrasound is 90-99% sensitive but may miss subserosal or small fibroids
◦ Addition of sonohysterography or hysteroscopy improves sensitivity for detecting submucosal fibroids

Treatment

Asymptomatic patients – clinical surveillance
Symptomatic:
• Premenopause:
◦ Patient wishes to preserve fertility
‣ NSAIDs
‣ Oral contraceptives
‣ Levonorgestrel releasing intrauterine system (Mirena)
‣ Gonadotropin releasing hormone agonist
‣ Selective progesterone receptor modulator
‣ Surgical therapy – myomectomy (surgical or endoscopic excision of tumors)

Patient who wishes to preserve uterus
‣ Medical
‣ Surgical
• Uterine artery embolization – interventional radiologic procedure to occlude uterine arteries
• Magnetic resonance guided focused US surgery – in situ destruction by high intensity US waves
• Myomectomy

Sources:
https://www.nichd.nih.gov/health/topics/uterine/conditioninfo/people-affected
https://www.sciencedirect.com/science/article/abs/pii/S1521693408000217?via%3Dihub

 

Day 2

The various antiemetic that are used include antihistamines, anticholinergic agents, dopamine antagonists, serotonin antagonists (5 HT3 antagonists) and other agents such as Dexamethasone, methylprednisone and trimethobenzamide.

There are three primary pathophysiologic pathways involved in the stimulation of the physiologic vomiting center in the medulla that directly mediates nausea and vomiting. This center can be stimulated by vestibular fibers, afferent visceral fibers, and input from the chemoreceptor trigger zone in the base of the fourth ventricle. The neurotransmitters histamine, acetylcholine, serotonin, and dopamine frequently are implicated in these pathways and are the targets of most therapeutic options.

An antihistamine agent that is commonly used is Dimenhydrinate (Dramamine), which is an OTC medication. Antihistamines inhibit the action of histamine at the H1 receptor, and limit stimulation of the vomiting center from the vestibular system (which is rich in histamine and acetylcholine). Dramamine is indicted for the prevention of nausea, vomiting and dizziness caused by motion sickness. The onset is about 20-30 min when administered IM, 15-30 min PO, and almost immediately when given IV. It’s duration is 3-6 hours and is extensively metabolized in the liver.

An anticholinergic agent that is used is Scopolamine, which inhibits the action of acetylcholine at the muscarinic receptor. These agents prevent motion-induced nausea and vomiting by blocking transmission of choleric impulse from vestibular nuclei to higher centers in CNS and from reticular formation to vomiting center. Scopolamine is indicated for nausea and vomiting, motion sickness, and as prophylaxis for nausea and vomiting associated with anesthesia, and chemotherapy induced nausea and vomiting. It can be applied as a transdermal patch or be administered by IV, IM or SC. The peak plasma time is 24 hours when transdermal. The duration when given IM is 4-6 hr, and 1-2 hours when given by IV. These. Agents are also metabolized by the liver.

Dopamine antagonists that are used as antiemetics include Chlorpromazine, Droperidol, Metoclopramide (Reglan), Prochlorperazine, and promethazine. These agents minimize the effect of dopamine at the D2 receptor in the chemoreceptor trigger zone, thereby limiting emetic input to the medullary vomiting center.
Metoclopramide is indicated for chemotherapy induced nausea and vomiting, diabetic gastroparesis, GERD, and postoperative nausea and vomiting. It is administered IV, IM and PO, and lasts 1-2 hours regardless of route, and it metabolized by the liver.

Although these agents are inexpensive and have diffuse efficacy, they have extensive side effects, such as sedation, orthostatic hypotension and extrapyramidal symptoms such as tar dive dyskinesia. Due to this, serotonin antagonists have replaced these agents for many indications.

Selective serotonin antagonists include Dolasteron, granisetron, and ondanstron (zofran). These agents inhibit the action of serotonin at the 5 HT3 receptor in the small bowel, vagus nerve, and chemoreceptor trigger zone. This action subsequently decreases afferent visceral and chemoreceptor trigger zone stimulation of the medullary vomiting center.
Zofran is indicated as prophylaxis for chemotherapy induced nausea and vomiting, postoperative nausea and vomiting and hyperemesis Gravidarum. It is administered IV, IM and PO, with an onset of 30 min and mainly metabolized in the liver.
Because of their diffuse blockade of serotonin, these agents have become the primary treatment for a variety of causes of nausea.

Dexamethasone (Decadron) • Methylprednisolone (Medrol)
Antiemetic MOA is not known, but thought to involve blockade of prostaglandins
Effective against mildly to moderately emetogenic chemotherapy, when used alone
Useful also in PONV
Used mainly in combination with other agents
• Adverse effects
Insomnia, agitation, appetite stimulation, GI symptoms

Antiemetic Use During Pregnancy
• Persistent nausea and vomiting of pregnancy (NVP)
First line therapy: Pyridoxine (10-25 mg QD to QID) with or without Doxylamine (12.5 mg-20 mg QD to QID.
• Persistent NVP with signs of dehydration
IV fluid replacement with thiamine Ondansetron, promethazine, and metoclopramide have similar effectiveness for hyperemesis gradidarum, Ondansetron may be better tolerated because of less AE