Moderate dosage estrogen-androgen therapy improves continuation rates in postmenopausal women: impact of the WHI reports.

OBJECTIVE: The purpose of this report is not to provide descriptive data for practice recommendations but to point the way to more liberal thinking than the conservatism of today. The patients in this historical practice, where moderate dosages of estrogen are used, with androgens added when indicated, continue hormone replacement therapy (HRT) for many years. These women were audited to determine the reasons for continuance. DESIGN: During the 3 years from 1996 to 1999, 814 women have been followed prospectively, the date of this first visit recorded, as well as the date last seen, the years of hormone use, and their current hormone replacement, so that continuation rates could be determined. The records of the patients were reviewed in January 2005 to determine the impact of the Women's Health Initiative (WHI). RESULTS: Of the 814 patients, there were 573 surgically menopausal women with a mean age of 61.8+/-3.25 years and 241 naturally menopausal women with a mean age of 58.6+/-3.08 years. During the 3 years of observation, 692 women continued HRT while 122 discontinued their therapy. Of those continuing therapy, 606 were treated with the implantation of various combinations of estradiol and testosterone pellets, while 86 used injectables, patches or oral hormones. Continuation rates for pellet patients were 96.7% for 10 years, 88.8% for 20 years, and 21.9% for 40 or more years. Continuation rates for the other hormone users were 53.5% for 10 years and 20.9% for 20 years. Eighty-one percent of the patients were prescribed progestogens, and 18 different progestogens or dosages or regimens were used to individualize therapy and provide as side-effect-free a regimen as possible. Continuation rates in the 692 remaining patients declined to 66.7% during the next 5 years. CONCLUSIONS: Moderate dosages of estrogens, with androgens added when indicated, improve continuation rates. Therapy must be individualized so that not only are menopausal symptoms relieved but also side-effects are minimal and women continue to feel good. The implantation of estradiol and testosterone pellets is not necessary for even the majority of postmenopausal women. However, estrogen dosages must be adequate to provide a sense of well-being. After the WHI reports, continuation rates declined more rapidly.

Estrogen replacement therapy in women with previous breast cancer.

OBJECTIVE: We sought to review the status of patients with breast cancer who were treated with estrogen replacement therapy and compare the results with those of nonestrogenic hormone users and women not treated with hormone replacement. STUDY DESIGN: The study group consisted of 76 patients with breast cancer, including 50 using estrogen replacement for up to 32 years, 8 using nonestrogenic hormone replacement for up to 6 years and followed for up to 11 years, and 18 using no hormones for up to 10 years. In addition to estrogen use, 40 of the 50 hormone users were treated with androgens, usually in the form of implantation of testosterone pellets. Forty-five subjects were also given progestogens, usually megestrol acetate 20 to 40 mg for 10 to 25 days each month. The 8 nonestrogen hormone users were treated with various combinations of testosterone pellets, tamoxifen, and progestogens. Forty-two of the 50 estrogen users are still being treated in our clinic, as are 2 of the 8 subjects using nonestrogen hormone. Follow-up was done through the tumor registry at University Hospital, and those whose tumor records were not current were telephoned. RESULTS: Of the 50 estrogen users, 3 have died (a mortality rate of 6%), and the rest have been followed for 6 months to 32 years, with a mean duration of follow-up of 83.3 +/- 8.81 months. One of the 8 nonestrogen hormone users has died (a mortality rate of 12.5%), and the rest have been followed for 2 to 11 years, with a mean duration of follow-up of 72.0 +/- 5. 93 months. Six of the 18 women not using hormone replacement have died (a mortality rate of 33.3%), and the rest have been followed for 6 months to 10 years, with a mean duration of follow-up of 50.5 +/- 6.01 months. CONCLUSION: Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progestogens may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks, and controversies.

Cervical dilation with prostaglandin F2 alpha for first trimester abortion.

Mechanical cervical dilation in the first trimester has been associated with some risk of cervical injury and incompetence of the cervix resulting in premature labor and spontaneous abortion. Several chemical agents have been used in trying to prevent this mishap in the last few years. Prostaglandins have been shown to soften and dilate the cervix gradually. We evaluated the efficacy of (15S)-15-methyl-prostaglandin F2 alpha-methyl-ester suppositories in the softening and dilatation of the cervix in patients having elective first trimester abortion (seven to 14 weeks' pregnancy). The mean cervical dilatation (internal os) was 8.7 mm in patients who were seven to ten weeks pregnant and 9.8 mm in the group who were 11 to 14 weeks pregnant. The mean cervical dilation before prostaglandin administration was 1.7 mm for the external os; the internal os was closed. The side effects were minimal and well tolerated. Blood loss was also reduced in these patients.

Estradiol and progesterone receptors in estrogen-primed endometrium.

Estradiol and progesterone receptor levels were measured in endometrial samples obtained from patients who were on different dosages of estradiol therapy and from women in the late proliferative phase of a normal menstrual cycle. Samples of blood were collected at the time of biopsy, and the levels of estradiol, estrone, progesterone, follicle stimulating hormone, and luteinizing hormone were measured in the serum. The patients were divided into five groups. The first group (controls) consisted of patients in their late proliferative phase. The patients in groups two, three, and five were receiving estradiol in various doses by pellet therapy, along with a cyclic progestogen each month. The women in the fourth group also had implantation of estradiol pellets but failed to take the progestogen as advised. In our series, the levels of cytoplasmic estradiol and progesterone receptors were markedly elevated in the no progestogen group compared to the controls. There was no significant difference in the levels of the receptors in the groups which took the progestogen as advised.

PIP: Estradiol and progesterone receptor levels were measured in endometrial samples obtained from patients who were on different dosages of estradiol therapy and from women in the late proliferative phase of a normal menstrual cycle. Samples of blood were collected at the time of biopsy, and the levels of estradiol, estrone, progesterone, follicle stimulating hormone, and luteinizing hormone were measured in the serum. The patients were divided into 5 groups. The 1st group (controls) consisted of patients in their late proliferative phase. The patients in groups 2, 3, and 4 were receiving estradiol in various doses by pellet therapy, along with a cyclic progestogen each month. The women in the 4th group also had implantation of estradiol pellets but failed to take the progestogen as advised. In our series, the levels of cytoplasmic estradiol and progesterone receptors were markedly elevated in the no progestogen group compared to the controls. There was no significant difference in the levels of the receptors in the groups which took the progestogen as advised.

The fate of a large bolus of exogenous estrogen administered to postmenopausal women.

Seventeen postmenopausal women were given a bolus of conjugated estrogens (USP, Premarin), 17 beta-estradiol and estriol orally, intravenously or by pellet implantation, and circulating levels of estrone, estradiol and/or estriol were measured by radioimmunoassay at various intervals during a 48--72-h period. Oral administration resulted in a marked rise in serum estrone; parenteral administration resulted in a marked increased in serum estradiol. There was no significant fall in serum gonadotropins during this period. Following estriol administration orally, there was a decided elevation in estriol levels but minimal change in estrone and estradiol.

Update on the male and female climateric.

The gonadal steroids--estrogens and androgens--appear to have a mood-elevating, psychotonic effect. The improved sense of well-being and increased vigor probably is engendered by restoration of somatic efficiency and psychic equilibrium. 1. The male climacteric, as observed in a limited number of men, is associated with a low level of serum testosterone. The levels of follicle-stimulating hormone and luteinizing hormone are not elevated because estrogen concentration continues unaltered well into old age. Androgen replacement therapy often lessens fatigue, depression and headaches, and headaches, and improves libidinous drives. 2. In the aging female, many climatric symptoms other than those due to vasomotor instability were heretofore considered merely coincidental. Recent studies suggest that the metabolism of cerebral hormones is markedly influenced by endogenous and exogenous gonadal steroids. Thus, postmenopausal depression, headaches, and nervousness may be hormone-dependent symptoms. 3. The incidence of endometrial cancer is no greater and is probably less in estrogen-treated women than in women not treated with estrogen, if regular cyclic courses of an oral progestogen are added to the regimen.

Role of the hypothalamus in the aging woman.

Relationships between the hypothalamus and the pituitary in the aging woman are discussed under the following subheadings: synthesis and release of follicle-stimulating and luteinizing hormones, estrogen receptors, other releasing factors, neurotransmitters, and the mechanisms of hot flushes and migrainoid headaches. The hypothalamus is the main regulator of pituitary function. In the female the hypothalamic-pituitary axis appears to remain functionally intact well into old age.

The significance of adrenal and ovarian catheterization in patients with polycystic ovary syndrome.

A previously unreported series of 15 anovulatory hirsute women with polycystic ovaries made up this study. Each underwent left adrenal and left ovarian vein catherization. Blood samples were obtained from the ovarian, adrenal and peripheral veins to test the levels of testosterone, delta 4 androstenedione (delta 4A), dehydroepiandrosterone (DHEA), estradiol and/or total estrogens, before and after administration of human chorionic gonadotropin (ten cases) and adrenocorticotropic hormone (ACTH) (five cases). Following intravenous human chorionic gonadotropin administration, the only response seen was a slight rise in ovarian levels of delta 4A and DHEA; after intravenous adrenocorticotropic hormone stimulation, the adrenal levels of delta 4A, testosterone and DHEA rose significantly. Peripheral concentrations of testosterone and delta 4A were in the high normal range and DHEA levels were high normal or slightly above normal range.