An alternative to hysterectomy? GnRH analogue combined with hormone replacement therapy.

OBJECTIVE: To assess whether GnRH analogues are effective in relieving pelvic pain and congestion and whether menopausal symptoms caused by GnRH analogues can be minimised by supplementation with low dose continuous combined hormone replacement therapy (HRT). DESIGN: Open prospective study. SETTING: Tertiary referral clinic at a teaching hospital. PATIENTS: Twenty-one women with chronic pelvic pain. INTERVENTION: Four months' therapy with goserelin 3.6 mg/month combined with continuous oestradiol valerate 1 mg daily and medroxyprogesterone acetate 5 mg daily. MAIN OUTCOME MEASURES: Visual analogue scale for pain, menopausal symptoms, bleeding patterns, uterine area, endometrial status, oestradiol concentrations and venogram scores. RESULTS: Amenorrhoea was maintained in all but two women. Endometrial atrophy was maintained despite HRT supplementation. Two women had moderate menopausal symptoms but none had severe symptoms. Significant reduction of uterine cross sectional area was maintained throughout the study. There was no significant relief of pain. CONCLUSIONS: HRT supplementation of GnRH analogues abolishes menopausal symptoms and thus may improve patient acceptability. Potentially beneficial effects such as endometrial atrophy, reduction of uterine volume and amenorrhoea were not negated by HRT. This combination is not effective in the treatment of chronic pelvic pain and congestion.

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.

Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause.

The protection afforded by postmenopausal oestrogen replacement against cardiovascular disease is not fully explained by changes in plasma lipoproteins. To investigate the effect of oestrogen on arterial tone, Doppler ultrasound was used to assess blood flow characteristics in the internal carotid arteries of 12 postmenopausal women. Patients were studied pretreatment and at weeks 4, 6, 9, and 22 of therapy with transdermal oestradiol 50 micrograms/day. The pulsatility index (PI), which is thought to represent impedance to blood flow distal to the point of sampling, was measured from the flow velocity waveform. 11 of the 12 patients were within 5 years of menopause; 1 was 8 years postmenopausal but had experienced bleeding 4 years after menopause. In the 11 women there was a highly significant correlation (r = 0.77) between time since menopause and baseline PI. A similar correlation (r = 0.74) was observed when the episode of postmenopausal bleeding was redefined as time of menopause in the twelfth patient. For all 12 patients, there was a significant negative correlation (r = -0.70) between change in PI during transdermal oestradiol therapy and mean of baseline plus week 22 PI value. For all correlations between changes in PI and time since menopause, the longer the time the greater the fall in PI. These results, and previous observations of a reduction in uterine artery PI with oestradiol treatment, suggest that oestrogen has a generalised effect on the arterial system.

Bilateral oophorectomy and hysterectomy in the treatment of intractable pelvic pain associated with pelvic congestion.

OBJECTIVE: To determine whether bilateral oophorectomy combined with hysterectomy is an effective treatment for chronic pelvic pain due to congestion. DESIGN: Prospective non-randomized single centre study. SETTING: Tertiary referral centre to a specialist pelvic pain clinic in a teaching hospital. SUBJECTS: 36 women, 33 of whom had failed to obtain long term relief of pain on medical therapy. MAIN OUTCOME MEASURES: Relief of pain, coital frequency, and effect on daily life. Histology of uterus and ovaries. RESULTS: Median pain score on visual analogue scale fell from a pre-operative value of 10 to 0 at one year. Twelve of the 36 women had some residual pain at one year postoperatively, but in only one woman was the pain affecting her daily life. Thirty women were noted to have pelvic tenderness pre-operatively, at one year, 26 had no tenderness and four minimal tenderness on pelvic examination. The median frequency of sexual intercourse increased from once per month preoperatively to eight times per month one year postoperatively. The uterus was histologically normal in 25 women, adenomyosis was present in eight of whom two had ovarian endometriosis. Fibroids were present in three and endometriosis was found confined to the ovaries in one woman. Multiple peripheral cysts were present in the ovaries of 25 women. CONCLUSION: Bilateral oophorectomy combined with hysterectomy and hormone replacement therapy is an effective treatment for chronic pelvic pain due to venous congestion, which has failed to respond to medical treatment and leads to restoration of normal coital function and daily life.

A risk-benefit assessment of estrogen therapy in postmenopausal women.

Estrogen therapy is extremely effective in relieving menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and certain psychological symptoms. The short term side effects from this therapy are usually mild and self-limiting. They are more common in women who commence hormone replacement therapy some years after the menopause than in those who start treatment at about the time of the ovarian failure. Pre-existing gynaecological conditions such as fibroids and endometriosis can be worsened by estrogen therapy. The majority of published studies suggest a beneficial effect of postmenopausal estrogen therapy on cardiovascular and cerebrovascular disease. These effects may be mediated by favourable changes in lipids, but other mechanisms may also be involved. It is uncertain whether the adverse changes in lipids caused by progestogen therapy will reduce any of the benefits of estrogen therapy on the cardiovascular system. Osteoporosis is the major bone disease of the Western world; long term estrogen therapy will prevent its development in most postmenopausal women. The risk of endometrial carcinoma is increased with unopposed estrogen therapy; this increased risk appears to be abolished if a progestogen is added at an adequate dose and duration for each cycle. The risk of ovarian or cervical cancer is not increased with estrogen therapy. There may be an increased risk of breast carcinoma with long term postmenopausal estrogen use, but the studies show inconsistent results.

Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women.

66 early postmenopausal women were randomised to 28-day cycles of either transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl-norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of 30 women were studied concurrently. Bone density was measured in the lumbar spine and proximal femur by dual photon absorptiometry at 6-month intervals for 18 months. Skeletal turnover was assessed by serum measurements of calcium, phosphate, and alkaline phosphatase, and by urine estimations of hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment groups by comparison with the untreated groups by comparison with the untreated group, bone density increased in the vertebrae and proximal femur and biochemical measurements indicated a significant reduction in bone turnover.

Prolonged endometrial stimulation associated with oestradiol implants.

OBJECTIVE: To provide information on endometrial stimulation after discontinuation of treatment with oestradiol implants. DESIGN: Long term follow up of withdrawal bleeding patterns in women taking progestogens cyclically every month after oestradiol implant treatment was ended. SETTING: Specialist menopause clinic. SUBJECTS: 10 Postmenopausal patients (at least 12 months' amenorrhoea after the last spontaneous period) who were treated with oestradiol implants for typical symptoms of oestrogen deficiency. The oestradiol dose was 50 mg, reimplantation occurring roughly every six months. Patients subsequently either needed to discontinue the hormone treatment for medical reasons or expressed a desire to stop treatment. MAIN OUTCOME MEASURE: Duration of endometrial stimulation--defined as the presence of withdrawal bleeding in response to progestogen given cyclically--after insertion of the last oestradiol implant. RESULTS: Four patients eventually stopped bleeding, their mean duration of bleeding being 35 months (range 27-43 months). One patient required hysterectomy 26 months after the last implantation because of persistent irregular bleeding despite treatment with high doses of progestogen. Three patients bled for 22, 30, and 36 months and then restarted oestrogen treatment because symptoms returned. The last two patients subsequently continued to bleed 12 and 21 months after the last implantation. CONCLUSIONS: The duration of endometrial stimulation after implantation can be prolonged, up to 43 months. Insertion of oestradiol implants can carry a long term commitment to the cyclical administration of progestogen and regular withdrawal bleeding if endometrial hyperplasia and carcinoma are to be avoided.