Treatment Of Severe Premenstrual Syndrome Research Articles

Is Premenstrual Syndrome a Uterine Inflammatory Disease? Retrospective Evaluation of an Etiologic Approach

Objective: To retrospectively evaluate the efficacy of local uterine antibiotic and anti-inflammatory injections combined with cryotherapy for the treatment of severe Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD). To validate the hypothesis of a uterine infectious/inflammatory etiology of PMS/PMDD. Methods: Clinical files of 161 women sequentially treated from September 1995 to April 2005, were collected for study. A subset of 148 patients (mean: 36.7 ± 7.8 years, range: 20.1 - 53.8 years) were eligible for statistical analysis. The ten most relevant PMS symptoms, namely depression, irritability, anxiety, fatigue, headache, edema, breast tenderness, abdominal bloating, pelvic pain and dysmenorrhea, were self-rated before and three menstrual cycles after treatment, using a 0 to 5 scale. The treatment consisted of cervical stromal antibiotic/anti-inflammatory injections combined with intracervical cryotherapy. Scores were compared using non-parametric tests for matched samples. Results: Before treatment, mean severity scores for the 10 symptoms were 3.97 ± 1.17, 4.26 ± 0.88, 3.41 ± 1.23, 3.91 ± 0.94, 3.35 ± 1.71, 2.28 ± 1.69, 2.13 ± 1.63, 4.51 ± 0.63, 2.28 ± 1.30, and 2.28 ± 1.88, respectively. Mean values after treatment were 0.54 ± 0.91, 0.51 ± 0.91, 0.32 ± 0.70, 0.42 ± 0.74, 0.43 ± 0.96, 0.22 ± 0.53, 0.39 ± 0.73, 1.01 ± 0.94, 0.28 ± 0.69, and 0.44 ± 0.92. All tests were statistically significant (p < 0.01). Conclusion: Both PMS physical and psycho-affective symptoms respond to local anti-inflammatory and antibiotic treatment of the uterus, showing a stable improvement after the treatment has ended. The results of this study suggest that the clinical pattern of PMS can be explained as an inflammatory mediated response to uterine infectious or traumatic insults. Further evidence is urgently needed in order to validate this innovative approach for widespread use in severe PMS/ PMDD cases.

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Suppression of cyclical ovarian function in the treatment of severe premenstrual syndrome

Suppression of cyclical ovarian function in the treatment of severe premenstrual syndrome

Hysterectomy and bilateral oophorectomy for severe premenstrual syndrome.

Premenstrual syndrome (PMS) is a chronic, poorly understood psycho-endocrine disorder severely affecting 5%; of women. Hormonal therapy which suppresses ovulation is the mainstay of medical treatment, but these interventions are rarely permanent. We evaluated the effectiveness and patient satisfaction with total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO) in PMS sufferers, and assessed the post-operative HRT continuation. All women undergoing TAH/BSO for severe PMS between January 1994 and April 2000 were interviewed and responses recorded by structured questionnaire. Forty-seven women were interviewed. Median age was 42 years (interquartile range 39.8-46.6) at the time of surgery. They had suffered with PMS for a mean of 9.68 years (SD 6.8) and received treatment for a mean of 3.57 years (SD 2.0) prior to referral to a gynaecologist. Fifty-two percent were treated with estradiol patches and 48% with estradiol implants prior to TAH/BSO. Ninety-six percent of women were 'satisfied' or 'very satisfied' with TAH/BSO, and 93.6% declared complete resolution of their cyclical symptoms; 93.6% were continuing with HRT usually by implants of estradiol and testosterone for a mean duration of 3.8 years (SD 1.86) post-operatively. Despite few reports of TAH/BSO as a treatment for severe PMS, we have found surgery, coupled with appropriate HRT, to be an extremely effective and well-accepted permanent cure for PMS.

A Pilot Naturalistic Follow-up of Extended Sertraline Treatment for Severe Premenstrual Syndrome

Freeman, Ellen W. PhD*†; Sondheimer, Steven J. MD*; Rickels, Karl MD*†; Martin, PG MS* Author Information

Use of leuprolide acetate plus tibolone in the treatment of severe premenstrual syndrome

Objective: To evaluate the effectiveness of GnRH agonist (GnRH-a) plus tibolone in the treatment of severe premenstrual syndrome (PMS). Design: Prospective, double-blind, placebo-controlled clinical trial. Setting: Department of Obstetrics and Gynecology, University of Naples “Federico II,” Naples, Italy. Patient(s): Thirty patients affected by severe PMS, aged 23–29 years (mean age ± SD, 25.3 ± 2.9 years). Intervention(s): Treatment for two cycles with leuprolide acetate depot (3.75 mg IM for 28 days) in association with tibolone (2.5 mg/d orally) or placebo (1 tablet per day orally). Main Outcome Measure(s): The mean severity of each symptom and sign of PMS was evaluated using a visual analog scale during the last 7 days of each treatment cycle in comparison with the last 7 days of the cycle before treatment. Result(s): Mean scores for each of the adverse psychological/physical and positive psychological symptoms were significantly improved during treatment. No statistically significant difference was detected between patients treated with tibolone and placebo. A significantly lower number of hot flushes per day was observed in groups treated with GnRH-a and tibolone in comparison with GnRH-a and placebo. Conclusion(s): Tibolone administered in association with GnRH-a does not reduce the therapeutic effect of GnRH-a in women affected by PMS. Tibolone used in association with GnRH-a may provide long-term medical treatment for women with PMS.

Prevalence of sexual abuse history in a sample of women seeking treatment for premenstrual syndrome

This study evaluated the prevalence and correlates of sexual abuse history among women seeking treatment for severe premenstrual syndrome (PMS). Of 77 women participating in a randomized clinical trial of non-pharmacological treatments for severe PMS, 42 were interviewed regarding their sexual abuse history. The interviewed women were a mean of 38 years old, and most were of European ancestry, heterosexual, married, employed and well-educated. At least one attempted or completed sexual abuse event was reported by 95% of the women, with 81 % reporting completed penetration against their will and 85% of these sustaining physical threat or harm. Compared to prior studies of sexually abused women in general populations, these women were abused earlier in life, more frequently and by similar types of offenders. Most of the abused women (65%) were estimated to have post-traumatic stress disorder (PTSD). Most abused women (83 %) had never disclosed the abuse to a health practitioner. The findings suggest that a history of sexual abuse, particularly in childhood or adolescence, may be extremely common among women seeking treatment for severe PMS, and that substantial undiagnosed PTSD may also be present in this population. Implications for patient screening and treatment are discussed.

The treatment of severe premenstrual syndrome with goserelin with and without ‘add-back’ estrogen therapy: A placebo-controlled study

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting ,60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily) ,Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2 ,4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2 ,4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2 ,4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

A double-blind trial of four medications to treat severe premenstrual syndrome

Objective: To determine the efficacy of fluoxetine (10 mg), alprazolam, propanolol and pyridoxine in the treatment of severe premenstrual syndrome (PMS). Method: One-hundred and twenty women were divided into four groups of 30 patients. Patients were submitted to a randomized, double-blind, placebo-controlled treatment and were given 3 months of placebo and 3 months of active drug. The active drug was pyridoxine (300 mg/day) in group 1; alprazolam (0.75 mg/day) in group 2; fluoxetine (10 mg/day) in group 3; and propanolol (20 mg/day and 40 mg during the menstrual period) in group 4. Results: Fluoxetine in 10-mg doses obtained a mean reduction of 65.4% in symptoms, followed by propanolol (58.7%), alprazolam (55.6%), pyridoxine (45.3%) and placebo (39.4–46.1%). Conclusion: Fluoxetine in 10-mg doses presented the best results for treating premenstrual syndrome.

A Double-blind Trial of Oral Progesterone, Alprazolam, and Placebo in Treatment of Severe Premenstrual Syndrome

To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.

A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome

A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome

A randomised comparison over 8 months of 100 μg and 200 μg twice weekly doses of transdermal oestradiol in the treatment of severe premenstrual syndrome

To determine the efficacy of a 100 micrograms twice weekly dose of Estraderm TTS compared with a 200 micrograms dose in the treatment of severe PMS, and to determine the overall acceptability of the treatment. To determine the serum oestradiol levels produced by the two doses of Estraderm and to discover whether the lower dose suppresses ovulation. Main: randomised, prospective, comparative study. Subsidiary: cross-sectional and prospective. Premenstrual syndrome clinic in teaching hospital. Women with severe PMS confirmed by prospective daily symptom recording. Estraderm TTS at a dose of either 100 or 200 micrograms twice weekly continuously with either dydrogesterone 10 mg or medroxyprogesterone acetate 5 mg, from day 17 to day 26 of each cycle. Main: change in total, exponentially smoothed, average maximum score (total-ESAmax) of 10 common premenstrual syndrome symptoms derived from Trigg's trend analysis and patient satisfaction. Subsidiary: plasma oestradiol and day 21 progesterone levels. Main: no difference in change in total-ESAmax between Estraderm 100 micrograms and 200 micrograms groups. Greater drop-out rate and greater incidence of side effects attributed to oestrogen in higher dosage group. Satisfaction rate of 45% to 57% at eight months. Subsidiary: 1. Mean (95% CI) oestradiol level of 300 pmol/l (255 to 345) with Estraderm 100 micrograms and 573 (494 to 693) with Estraderm 200 micrograms; 2. Estraderm 100 micrograms suppresses mid-luteal progesterone from a mean (95% CI) of 35.5 (28.4 to 42.7) to 3.4 (2.4 to 4.5). Estraderm TTS 100 micrograms twice weekly is as effective as 200 micrograms twice weekly in reducing symptom levels in severe premenstrual syndrome but is better tolerated. Estraderm 100 micrograms suppresses ovulation and results in a mean plasma oestradiol level similar to that observed in a spontaneous cycle.

Successful Treatment of Severe Premenstrual Syndrome by Combined Use of Gonadotropin-Releasing Hormone Agonist and Estrogen/Progestin

Department of Reproductwe Medcme, Unrvers/ty of Calrfomia-San Drego School of Medcme (T-002), La Jolla, Cakfornra J Clin Endocrinol Metab 77 252A, 1991

Low dose danazol in the treatment of the premenstrual syndrome

This double-blind, randomized, crossover study compared the efficacy and safety of danazol (100 mg twice daily) with matching placebo in the treatment of severe premenstrual syndrome. Nineteen patients were randomly allocated to receive danazol for 3 months followed by placebo, and 18 to receive treatment in the reverse order. Assessments of overall condition showed improvement to be statistically significantly more likely with danazol than with placebo (P less than 0.001) after 3 months' treatment. Furthermore, daily visual analogue scale assessments demonstrated statistically significantly better premenstrual scores with danazol in comparison to placebo for breast discomfort, irritability, depression, anxiety, mood swings, crying, depressed libido and abdominal swelling. It is concluded that danazol provides effective and generally well tolerated treatment for severe premenstrual syndrome.

Successful Treatment of Severe Premenstrual Syndrome by Combined Use of Gonadotropin-Releasing Hormone Agonist and Estrogen/Progestin*

Although abolishment of ovarian cyclicity by the use of a long-acting GnRH agonist (GnRH-a) provides effective treatment for premenstrual syndrome (PMS), its use is limited by sequellae of the resultant hypoestrogenism. In this study the effects of estrogen/progestin replacement on the symptomatic improvement afforded by GnRH-a were evaluated in eight women with severe PMS. The 8-month study design included 2 months of control, 2 months of GnRH-a alone, and 4 further months in which the exogenous steroids were replaced in randomized, double blind, placebo-controlled cross-over fashion using 1 month each of 1) conjugated equine estrogen (CEE) on days 1-25, 2) 10 mg medroxyprogesterone acetate (MPA) on days 16-25, 3) CEE (days 1-25) plus MPA (days 16-25), and 4) placebo alone. Mood and physical symptoms were measured daily on a valid and reliable instrument, the Calendar of Premenstrual Experiences. As expected, administration of GnRH-a alone resulted in a 75% improvement in luteal phase symptom scores (17.8 +/- 4.8 vs. 4.2 +/- 1.6; P less than 0.01). Combined sequential administration of CEE and MPA in addition to GnRH-a was effective in maintaining the reduced symptom scores seen after GnRH-a alone and was superior to the addition of CEE alone, MPA alone, or placebo. This combination of CEE and MPA resulted in a 60% improvement (P less than 0.05) compared to the luteal phase of control months in both behavioral (14.1 +/- 3.9 vs. 4.2 +/- 0.8) and total (17.8 +/- 4.8 vs. 6.5 +/- 1.8) symptoms. We conclude that the undesirable consequence of ovarian steroid deficiency in the treatment of PMS by GnRH-a can be overcome by the addition of sequential estrogen and progestogen replacements without significantly reducing the effectiveness of GnRH-a in this disorder.