Lecture 11- Menstrual and Menopause Disorders

Menstrual & Menopause Disorders Noha El Baghdady, Ph.D.  The premenstrual syndrome (PMS) & The premenstrual dysphoric disorder (PMDD) ‫ او اﻛﺛر ﻣن اﻻﻋراض ﻓﻲ اﻟﻔﺗره اﻟﻠﻲ ﻗﺑل اﻟدورة‬٥ ‫ﻻزم ﯾﻛون ﻓﻲ ﺗﻘرﯾر ﻟﻣده ﺳﻧﺔ ل‬ ‫ﻋرض واﺣد ﻛﻔﺎﯾﺔ ﺑﯾﺗﻛرر ﺷﮭرﯾﺎ ﻟﻣده ﺷﮭرﯾن ﻟو اﻛﺛر طﺎﻟﻣﺎ...

Menstrual & Menopause Disorders Noha El Baghdady, Ph.D.  The premenstrual syndrome (PMS) & The premenstrual dysphoric disorder (PMDD) ‫ او اﻛﺛر ﻣن اﻻﻋراض ﻓﻲ اﻟﻔﺗره اﻟﻠﻲ ﻗﺑل اﻟدورة‬٥ ‫ﻻزم ﯾﻛون ﻓﻲ ﺗﻘرﯾر ﻟﻣده ﺳﻧﺔ ل‬ ‫ﻋرض واﺣد ﻛﻔﺎﯾﺔ ﺑﯾﺗﻛرر ﺷﮭرﯾﺎ ﻟﻣده ﺷﮭرﯾن ﻟو اﻛﺛر طﺎﻟﻣﺎ ﺑﺗﺄﺛر ﻋﻠﻰ ﺣﯾﺎﺗﮭﺎ‬ The premenstrual dysphoric disorder The premenstrual syndrome (PMS) (PMDD) The American Psychiatric Association (APA) defines premenstrual dysphoric disorder PMS is characterized by the (PMDD) as a severe form of PMS in presence of both physical and which symptoms of anger, irritability, and internal tension are behavioral symptoms that occur prominent. repetitively in the second half of The mood and physical symptoms the menstrual cycle and are typically most severe (and interfere with some aspects of accompanied by functional the woman's life. impairment) in the four days before through the first two to three days of menses  Not-premenstrual syndrome (PMS) Most women of reproductive age experience one or more mild emotional or physical symptoms for one to two days before the onset of menses The symptoms (such as breast soreness and bloating) are mild, do not cause severe distress or functional impairment, and are not considered to represent premenstrual syndrome (PMS)  Most common symptoms 1. Behavioral Symptoms 2. Physical manifestations The most Most common: Abdominal bloating common affective or behavioral sym and an extreme sense of fatigue. -ptom of PMS is mood swings. Other common symptoms include: Others (infrequent): breast tenderness, headaches, hot Irritability, anxiety/tension, sad or flashes, and dizziness. depressed mood, increased appetite/food cravings, sensitivity to rejection, and diminished interest in activities. Timing of symptoms For most women, the types of symptoms are fairly consistent across cycles and last for an average of six days per month. Diagnosis Natural history (PMS symptoms) Begin any time after menarche, but usually by one's early 20s, and typically continue throughout reproductive life (if untreated). Some women experience more severe symptoms in the late reproductive years Women with premenstrual disorders appear to be at higher risk for developing mood disorders during the menopausal transition. PMS resolves completely after menopause and transiently during pregnancy Diagnosis Physical exam There are no specific abnormalities on physical exam in women with PMS/PMDD. Laboratory findings There are no specific biochemical abnormalities associated with the disorder. but we make ot to exclude other diseases (e.g depresssion) Assessment ‫ﺑﺗﺣﺻل ﻟﻣده ﺷﮭرﯾن ﻣﺗﺗﺎﻟﯾن‬ The assessment of patients with possible premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) should include the following: 1. A detailed menstrual history, because the relationship between symptoms and cycle phase must be confirmed. 2. If the patient's cycles are regular (25to35 days intermenstrual interval) Detailed information about her symptoms should then be obtained (Type, pattern of onset and offset, severity, presence of functional impairment, and confirmation that symptoms are recurrent). Assessment 3. Women with PMS/PMDD may also experience irregular menstrual cycles (35 days) particularly during the menopausal transition. In this setting, symptoms may be more difficult to track because of cycle variability. 4. Biochemical testing is not required in women with irregular cycles during the transition but should be performed in younger women to determine the etiology of the irregular menstrual cycles. Serum human chorionic gonadotropin (hCG), thyroid-stimulating hormone (TSH), prolactin, and follicle-stimulating hormone (FSH) measurement is recommended. Assessment 5- Hormones A serum TSH to rule out hyper- and hypothyroidism, both of which can cause mood symptoms. 6- The existence of a chronic, mild mood disorder such as Persistent depressive disorder or major depressive disorder should be ruled out. If the patient's symptom history is consistent with PMS/PMDD and there is no evidence of other medical disorders, the patient should be asked to record symptoms prospectively for two months to confirm the diagnosis. Assessment 7- Evaluation of medications Hormonal treatment –oral contraceptives. Of note, OCs are sometimes used to treat premenstrual disorders, although they are not considered a first-line therapy. Diagnosis The American College of Obstetricians and Gynecologists (ACOG) define PMS as: “The presence of at least one symptom occurring in the luteal phase of the cycle, which leads to impairment in functioning.” The symptom(s) must impair functioning in some way and the symptom must remit at menses or shortly thereafter to constitute a symptom-free interval. APA DSM-5 system The American Psychiatric Association APA DSM-5 system, which provides premenstrual dysphoric disorder (PMDD) criteria. These criteria require: 1. Prospective documentation of physical and behavioral symptoms (using diaries) being present for most of the past year. 2. Five or more symptoms must have been present during the week prior to menses, resolving within a few days after menses starts. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria DSM-5 criteria One or more of the following symptoms One or more of the following symptoms must be present to reach a total of five must be present symptoms overall Difficulty concentrating Change in appetite, food cravings, Mood swings, sudden sadness, increased overeating sensitivity to rejection Diminished interest in usual activities Anger, irritability Easy fatigability, decreased energy Sense of hopelessness, depressed mood, Feeling overwhelmed or out of control self-critical thoughts Breast tenderness, bloating, weight Tension, anxiety, feeling on edge gain, or joint/muscles aches Sleeping too much or not sleeping enough Management  Mild Symptoms Exercise and relaxation techniques Exercise and stress reduction are beneficial in general and should be recommended on this basis. Dietary Supplement Vitex agnus castus — Vitex agnus castus (chasteberry) is a popular herbal remedy that appears to be an effective treatment option for women with mild premenstrual symptoms. Dietary Supplement Primrose oil, vitamin B6, vitamin E, calcium, and magnesium, have been studied as therapeutic agents for PMS. The routine use of vitamin B6, high doses of calcium supplements, or other vitamins given the low-quality evidence and the potential for harm (peripheral neuropathy with high-dose B6 and an increased risk of renal calculi and possible risk of heart disease with calcium supplementation). Management (Moderate – Sever) because she is planing for pregnancy SSRI Of all the treatment options for PMDD, SSRIs have the best evidence for efficacy. Choosing a regimen 1. Continuously throughout the menstrual cycle 2. During the luteal phase only 3. At symptom onset Depends on a number of factors (1) The symptoms are present only during the premenstrual phase of the menstrual cycle versus throughout the menstrual cycle with premenstrual worsening (2) Patient preference (3) Predictability of symptom expression Choosing a regimen Dosing of Citalopram for PMS/PMDD (Off-label) ‫ ﺑﺟرﻋﺔ ﻛل ﺷﮭر ﻟو اﺣﺗﺎﺟت‬10mg ‫ﻧﻔدر ﻧزود‬ mg 40 ‫ﺑس اﻟﺣد اﻻﻗﺻﻰ اﻧﮭﺎ ﺗﺎﺧد‬ Continuous daily dosing regimen – The initial dose in cycle one is 10 mg daily. The dose may be increased over the first month as needed to 20 mg daily. In subsequent menstrual cycles, further dose increases up to a maximum of 40 mg/day. Intermittent regimens Luteal phase dosing regimen The initial dose in cycle one is 10 mg daily starting on day 14 and continued until the onset of menses. The dose can increase over the first month to usual effective dose of 20 mg daily. In a subsequent cycle, a further increase to a maximum dose of 30 mg/day. A maximum dose of 40 mg/day for continuous regimens, but only 30 mg/day for intermittent regimens. Intermittent regimens Symptom-onset dosing regimen The initial dose in cycle one is 10 mg daily beginning the day of symptom onset until a few days after the start of menses Over the first month, the dose may be increased as needed to usual effective dose of 20 mg daily. In subsequent menstrual cycles, a further increase to the maximum intermittent regimen dose (30 mg/day). SSRI Common side effects Side effects of SSRIs are dose dependent Occur in approximately 15 % of patients and are the most common reason for discontinuing treatment. These include nausea, headache, insomnia, and decreased libido. Nausea, the most common side effect, usually resolves within four to five days and does not persist if treatment is given intermittently (luteal phase only). To minimize side effects, initiate therapy with a low dose and increasing as needed. must be gradually stooped SSRI side effects Sexual side effects The most problematic side effect of an SSRI may be sexual dysfunction, including diminished sexual interest, delayed orgasm, and anorgasmia. A dose reduction may not alleviate this side effect. Women should be informed that this complication may arise. Sexual function recovers after therapy is stopped. Intermittent (luteal phase) treatment may reduce these side effects. SSRI Discontinuation symptoms Continuous daily administration of SSRI for several months followed by sudden treatment discontinuation can lead to discontinuation symptoms such as dizziness, ringing of the ears, and mild "body shocks" Dose tapering to avoid withdrawal symptoms.  prefferen mono Combined estrogen-progestin contraception For women with moderate to severe symptoms who are interested in hormonal contraception, COC is recommended. Contraception This is the simplest way to suppress the hypothalamic-pituitary-ovarian axis and ovulation. Monophasic pills are preferred. Contraception Drospirenone-containing COCs are effective and approved for the management of PMDD. If symptom relief with the COC monotherapy is incomplete, an SSRI can be added. Start with a 3 mg drospirenone (DRSP)/20 mcg ethinyl estradiol (EE) COC.  Menopause & Perimenopause 2nd phase Menopause can happen naturally, or for reasons such as surgery (oophorectomy, hysterectomy), cancer treatments like chemotherapy, or a genetic reason, sometimes the reason is unknown. Perimenopause is when female has the symptoms of menopause, but menstruation have not stopped. Perimenopause ends with menopause when females has not had a period for 12 months.  ‫ﻣﻔﯾش دورة ﻟﻣدة ﺳﻧﮫ‬ Definition: Cessation of menstrual periods for 1 year, also known as final menstrual period, loss of ovarian follicular function Average age of menopause is 52 years, but ranges from 40 to 58 years.  MENOPAUSE (Common symptoms) a. Vasomotor symptoms (hot flashes) They may impact quality of life (need treatment) May interrupt sleep and cause Common symptoms include: insomnia Increased skin temperature Usually within 12–24 months Nausea Dizziness after the last menstrual period Headache (Occur in 75%–85% of Palpitations women). Diaphoresis Night sweats  MENOPAUSE (Common symptoms) b. Genitourinary syndrome of menopause (GSM) i. Decrease in estrogen and other sex steroids causes thinning of hair in the pubis region and shrinkage of the labia minora; vulvovaginal atrophy (VVA) leads to pruritus and pain. ii. Loss of lubrication leads to dyspareunia. iii. Vaginal pH changes and becomes more basic (from 4.5−5 to 6−8), creating a favorable environment for bacterial colonization. iv. Thinning of urethra and bladder lining and decreased muscle tone result in recurrent episodes of urinary frequency, urgency with dysuria, and urinary tract infections.  Treatments 1. Individualization of therapy is essential. 2. The patient’s medical history must be considered.  Treatments Required examination Elective examinations Thyroid function, breast History taking, physical ultrasonography, endometrial examination, liver function, kidney biopsy function, anemia, fasting blood Conducted at an interval of 1–2 sugar, serum lipid profile, years. mammography, BMD test, and Pap smear screening.  Treatments Hormone therapy (HT) FDA approved indications for HT Treatment of moderate to severe vasomotor symptoms “Estrogen and progestogen therapy (EPT), Treatment of moderate to severe GSM estrogen-only therapy (ET), progestogen*- Prevention of postmenopausal osteoporosis only therapy (PT), and estrogen-receptor Hypoestrogenism caused by hypogonadism (ER) agonists or antagonists.” Castration or premature ovarian failure. *(Progestogen is an umbrella term for progesterone [natural] and progestins [synthetic])  Recommendations for HT i. Menopausal symptom relief: (a) Moderate to severe vasomotor symptoms (primary indication) 1. Recommend lowest effective dose. 2. For women ≤ 60 or women who are within 10 years of menopause onset without contraindications or at a high risk of CVD or breast cancer, assess the baseline risk of breast cancer and CVD, and consider risk when making a recommendation. (b) Moderate-to-severe GSM 1. Vaginal symptoms – Recommend local ET therapy if treating vaginal symptoms only. 2. Urinary health – Systemic HT may worsen stress incontinence; local ET therapy may help with overactive bladder. but not always (c) Sexual symptoms – HT not recommended for sole treatment of diminished libido due to diminished libido  Recommendations for HT for manegment of osteoprosis for prevention of osteoprosis osteoprosis manegment ‫اﻻول ﻧﻌﺎﻟﺟﺔ ﺑﺎل‬ (If patioen is on high resk of osteoprosis) and hormonal therapy ‫ﻟو ﻣﺟﺎﺑش ﻧﺗﯾﺟﺞ ﻧروح ﻟل‬ (have vasomotor symptoms moderet to sever) hormonal therapy will help in this case (it will be 1st line treatment here) (d) Osteoporosis EPT and ET indication for prevention ↓ osteoporotic fractures Used only when alternative therapies are not appropriate ER agonists/antagonists may also be used for osteoporosis.  3 ‫ﻣﯾﻛوﻧش ﻋﻧدھﺎ ﺣﺎﺟﺔ ﻣن دول‬ ‫ﻟو ﺣد ﻣش ھﯾﻧﻔﻊ ﻧدﯾﻠﺔ‬ absolute contraindicaton of hormonal therapy ‫ﻻﻧﮫ دول‬ ‫ ؟؟‬hormonal therapy Formulations Oral: Used for vasomotor symptoms, also covers GSM if concomitant. Transdermal: For women who are intolerant of oral preparations, used for vasomotor symptoms, also covers GSM if concomitant; consider as first-line for women with moderate risk of CVD if estrogen is needed. Vaginal and local preparations: For women with GSM. Topical treatment is sufficient and should be tried before oral preparations for patients experiencing no other symptoms.  Serotonin reuptake inhibitors The Best for vasomotor symptoms in high-risk women for whom HT is not recommended. e.g.: Paroxetine 7.5 mg orally once daily (only selective serotonin reuptake inhibitor with indication for vasomotor symptoms) Venlafaxine 75 mg orally once daily Fluoxetine 20 mg orally once daily Escitalopram 10–20 mg orally once daily Citalopram 10–20 mg orally once daily  Natural products “Some data for effectiveness (no FDA indication)” a. Soy isoflavones: May still have adverse effects similar to those of conjugated estrogens. b. Evening primrose oil: No solid evidence for use. c. Black cohosh: Some effectiveness for vasomotor symptoms; reports of liver toxicity. Others Used for vasomotor symptoms (no FDA indication) a. Clonidine b. Gabapentin c. Pregabalin d. Acupuncture e. Lifestyle changes g. Hypnosis