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Biomedical subjects

M P Warren

Publications and source records attributed to M P Warren.

At least 19 recordsLinked to original sources
PubMed2004

The genetics, diagnosis and treatment of amenorrhea.

The menstrual cycle is regulated by complex feedback interactions between the ovaries, pituitary and hypothalamus. A disruption at any point in one of these pathways may lead to irregularities in the menstrual cycle. In particular, amenorrhea, the cessation of menstrual functioning, serves as an indicator of ovarian, pituitary and/or hypothalamic dysfunction. Historically, diagnosing and treating amenorrhea presented medical professionals with numerous practical difficulties. In recent years, however, studies of amenorrhea have yielded new understandings and new treatments of the disorder. This paper synthesizes these current methodologies for diagnosing, treating and understanding both primary and secondary amenorrhea.

Amenorrhea↗
PubMed2003

Exercise-induced endocrine pathologies.

There has been a substantial increase in women practicing sports over the past 30 yr. While exercise provides many health benefits, there appears to be a unique set of risks associated with intense exercise for the female athlete. The female athlete triad encompasses these risks, including amenorrhea, osteoporosis and eating disorders. The incidence of menstrual irregularities including primary and secondary amenorrhea and shortened luteal phases is much higher among women partaking in athletics, specifically in sports requiring low body weight for performance and aesthetics. The hormone pattern seen in these amenorrheic athletes includes a decrease in GnRH pulses from the hypothalamus, which results in decreased pulsatile secretion of LH and FSH and shuts down stimulation of the ovary. The recently discovered hormone leptin may also play a large role as a significant mediator of reproductive function. The prevalence of eating disorders is high among female athletes who practice sports which emphasize leanness. Consequently, the cause of menstrual irregularities is not due to the exercise alone, but to chronic inadequate or restrictive caloric intake that does not compensate for the energy expenditure. The most dangerous risk associated with amenorrhea for the female athlete is the impact on the skeleton. Complications associated with amenorrhea include compromised bone density, failure to attain peak bone mass in adolescence and increased risk of stress fractures. The diagnosis of exercise-associated menstrual dysfunctions is one of exclusion. The most effective treatment is to decrease the intensity of the exercise and increase the nutritional intake. Hormone replacement has also been under investigation as a possible treatment.

Adolescent↗
PubMed2003

Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea.

This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.

Adolescent↗
PubMed2001

Hypothalamic amenorrhea. The effects of environmental stresses on the reproductive system: a central effect of the central nervous system.

Although the treatment of anovulation has become significantly more specialized and complex in the centuries since Hippocrates, a complete understanding of the causes and mechanisms of hypothalamic amenorrhea has not been achieved. Even the best research on hypothalamic amenorrhea is plagued by the lack of longitudinal studies, the use of different exercise models, the difficulty of controlling for caloric intake, and the fact that genetics may have a role in the disorder. Continuing research on metabolic rate, leptin, and other factors will ultimately answer many of the outstanding questions and will help to create better tools for treating this disorder.

Amenorrhea↗
PubMed2001

Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study.

The objective of this study was to evaluate the psychological side effects of a transvaginal natural progesterone gel in hormone replacement therapy (HRT). This 3-month preliminary study was part of a multicenter study previously performed in our center. We enrolled 49 women (ages 18-45 years) with hypothalamic amenorrhea (HA) (n = 40) and premature ovarian failure (POF) (n = 9). Estrogenized patients applied vaginal progesterone gel (4% or 8%) every other day for six doses per month. The Hopkins Symptom Checklist (HSCL), a psychometric profile test, was administered at baseline, day 13 of cycle 2, day 24 of cycle 2, and day 24 of cycle 3. Application of the progesterone gel caused no significant change in HSCL total scores or individual symptom scores for somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety. Natural vaginal progesterone gel can be an effective alternative to oral progesterone for women on HRT.

Administration, Intravaginal↗
PubMed2001

Temporomandibular disorders and hormones in women.

Temporomandibular disorders (TMD) are loosely defined as an assorted set of clinical conditions, characterized by pain and dysfunction of the masticatory system. Pain in the masticatory muscles, in the temporomandibular joint (TMJ), and in associated hard and soft tissues, limitation in jaw function, and sounds in the TMJ are common symptoms. That women make up the majority of patients treated for TMD is extensively hypothesized and documented in numerous epidemiological studies. Certain contradictory studies exist which propose that there are no statistically significant gender differences in the actual incidence of changes in joint morphology. Nonetheless, extensive literature suggests the disorder is 1.5-2 times more prevalent in women than in men, and that 80% of patients treated for TMD are women. The severity of symptoms is also related to the age of the patients. Pain onset tends to occur after puberty, and peaks in the reproductive years, with the highest prevalence occurring in women aged 20-40, and the lowest among children, adolescents, and the elderly. The gender and age distribution of TMD suggests a possible link between its pathogenesis and the female hormonal axis. In this review, we will use the hypothesis that the overwhelming majority of patients treated for temporomandibular disorders are women and use the available literature to examine the role of hormones in TMD.

Contraceptives, Oral↗
PubMed2001

The effects of intense exercise on the female reproductive system.

Women have become increasingly physically active in recent decades. While exercise provides substantial health benefits, intensive exercise is also associated with a unique set of risks for the female athlete. Hypothalamic dysfunction associated with strenuous exercise, and the resulting disturbance of GnRH pulsatility, can result in delayed menarche and disruption of menstrual cyclicity. Specific mechanisms triggering reproductive dysfunction may vary across athletic disciplines. An energy drain incurred by women whose energy expenditure exceeds dietary energy intake appears to be the primary factor effecting GnRH suppression in athletes engaged in sports emphasizing leanness; nutritional restriction may be an important causal factor in the hypoestrogenism observed in these athletes. A distinct hormonal profile characterized by hyperandrogenism rather than hypoestrogenism is associated with athletes engaged in sports emphasizing strength over leanness. Complications associated with suppression of GnRH include infertility and compromised bone density. Failure to attain peak bone mass and bone loss predispose hypoestrogenic athletes to osteopenia and osteoporosis. Metabolic aberrations associated with nutritional insult may be the primary factors effecting low bone density in hypoestrogenic athletes, thus diagnosis should include careful screening for abnormal eating behavior. Increasing caloric intake to offset high energy demand may be sufficient to reverse menstrual dysfunction and stimulate bone accretion. Treatment with exogenous estrogen may help to curb further bone loss in the hypoestrogenic amenorrheic athlete, but may not be sufficient to stimulate bone growth. Treatment aimed at correcting metabolic abnormalities may in fact prove more effective than that aimed at correcting estrogen deficiencies.

Adolescent↗
PubMed2000

The female athlete.

Over the past 30 years, the number of women participating in organized sports has grown dramatically. Several forms of menstrual irregularities have been described in the female athlete: primary and secondary amenorrhoea, oligomenorrhoea, short luteal phases and anovulation. The incidence of menstrual irregularities is much higher in activities where a thin body is required for better performance. The hormonal pattern seen in these athletes is a hypothalamic amenorrhoea profile. There appears to be a decrease in gonadotrophin-releasing hormone (GnRH) pulses from the hypothalamus, which in turn decreases the pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and shuts down stimulation of ovary. Recently, another type of amenorrhoea has been described in swimmers which is characterized by mild hyperandrogenism. Athletes with low weight are at risk of developing the female athletic triad, which includes amenorrhoea, osteoporosis and disordered eating. Athletes with this triad are susceptible to stress fractures. Other issues include the pregnant athlete. Intensive exercise during pregnancy can cause bradycardia. Safe limits of aerobic exercise in pregnancy depend on previous exercise habits. Infertility, which may develop with exercise, is probably reversible with reduction of exercise or weight gain. High impact sports activities may produce urinary incontinence. Oestrogen replacement therapy is often prescribed in amenorrhoeic athletes, but bone loss may not be completely reversible.

Body Constitution↗
PubMed1999

A new clinical option for hormone replacement therapy in women with secondary amenorrhea: effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of 2 doses of a transvaginal polycarbophil-based progesterone gel (4% and 8%) in hormone replacement therapy. STUDY DESIGN: This multicenter, randomized, parallel-group, open-label 3-month study included 127 women with secondary amenorrhea. Estrogenized patients applied transvaginal progesterone (4% or 8%) every other day for 6 doses per month. Efficacy was based on endometrial biopsy findings and withdrawal bleeding. McNemar's test was used to compare incidence of adverse events before and during treatment. RESULTS: Progestational changes were found in 92% (Crinone 4%) and 100% (Crinone 8%) of patients with evaluable biopsies. Withdrawal bleeding was experienced by 81% (Crinone 4%) and 82% (Crinone 8%) of the patients. No patient experienced any serious side effect related to treatment. The incidence of most side effects, including psychologic symptoms, decreased with progesterone treatment compared with estrogen alone therapy. Compliance exceeded 98% for both doses. CONCLUSIONS: Crinone is a novel, effective, and well-tolerated option for hormone replacement therapy in women with secondary amenorrhea.

Administration, Intravaginal↗
PubMed1999

Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating.

Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated scores of abnormal eating twice those found in normal subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not significantly, whereas leptin values were significantly lower (P < 0.05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and the pathogenesis of osteopenia despite normal body weight. These findings suggest that the mechanism of amenorrhea and low leptin in these women results mainly from a metabolic/nutritional insult.

Adult↗
PubMed1999

Exercise and female adolescents: effects on the reproductive and skeletal systems.

It is generally accepted that exercise is beneficial for young women, since it increases cardiovascular fitness and reduces adiposity. Too much exercise can have negative effects on the reproductive and skeletal systems, however, including primary and secondary amenorrhea thought to be caused by several factors including low body weight and improper nutrition. Primary and secondary amenorrhea present similar patterns of luteinizing hormone and follicle stimulating hormone suppression, probably involving the hypothalamic-pituitary-gonadal axis and possibly also the hypothalamic-pituitary-adrenal axis. Recent research has also suggested that leptin (a hormone made by the fat cell) is a possible link between menstrual cycles and fat and energy levels. The female athletic triad consists of three interrelated problems: eating disorders, amenorrhea, and osteopenia. The most serious aspect of hypoestrogenism is its effect on bone growth of elite athletes; those with delayed menarche show a higher incidence of scoliosis, stress fractures, and osteopenia than do girls with normal menarche. The higher incidence of bone problems may be linked to a lower rate of bone accretion, which may lead to lower peak bone mass. Unfortunately, the loss may be irreversible. In addition to decreasing training and gaining weight, treatment for menarcheal delay may include oral contraceptive therapy.

Adolescent↗
PubMed1998

Primary dysmenorrhea and physical activity.

It has been widely claimed that exercise is beneficial to dysmenorrhea, yet solid evidence is lacking. Studies investigating this relationship have been reviewed for this paper. Most showed decreased prevalence and/or improved symptomatology with exercise. However, controlled longitudinal studies involving women with confirmed primary dysmenorrhea who are sufficiently blinded to the study objectives are necessary before a definite relationship between exercise and dysmenorrhea can be established.

Adolescent↗