Why treat Ovarian Failure?
The ovaries are endocrine organs that are regulated by the pituitary gonadotrophins Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) to produce estrogen, progesterone and androgens which, in addition to being responsible for the development of secondary sex characteristics and the regulation of the reproductive cycle, have important implications for the health and well being of women. To say that ovarian failure is a “natural” condition that marks a normal life transition of women is to say that the only function the ovaries serve is a reproductive one and once this function has been completed, there is no further need for ovarian hormones. The presence of estrogen, progesterone and androgen receptors throughout the body within brain, bone, muscle, endometrium, periodontium and mucous membranes including the genitourinary tract and and buccal cavity would suggest otherwise. Except for the appendix, there are no vestigial organs so when ovarian functioning is lost, there will be negative ramifications for a woman’s overall health.
Since most women today can expect to live about 1/3 of their lives after cessation of ovarian function, it is important to consider how the effects of ovarian hormone deficiencies affect quality of life and general medical health. Ovarian failure is a chronic illness that should be recognized and women who present with symptoms should be offered appropriate therapeutic replacement therapy. Such a concept requires a paradigm shift in thinking for both medical professionals and the general public about this life transition experienced by all women generally between the ages of 48-55 years that heretofore has been considered a natural life transition whose symptomatology is to be accepted and endured.
What happens to brain, bone, muscle, vascular walls, periodontium, oral and urogenital mucous membranes after ovarian failure? Epidemiologic studies clearly show that women’s risk of cardiovascular disease quickly approaches the same risk as men after cessation of ovarian function, although this relationship is complex and involves multiple other risk factors. Post ovarian failure osteoporosis with loss of periodontium, the supporting structure of teeth, is a recognized dental sequela of ovarian failure. As women age, they are more than twice as likely as men to be afflicted with Alzheimer’s Disease (AD). Ovarian failure has a direct impact on tissue changes and the microflora in the vulva and vagina including loss of collagen and thinning of the surface epithelium, making it more friable, less elastic, more alkaline and thus predisposed to enteric bacterial colonization. Such atrophy and alkalinization of the vaginal epithelium can lead to dyspareunia and vaginitis symptoms. A longitudinal population study done by Dennerstein, et al found that 3% of premenopausal women reported vaginal dryness versus 25% of women postmenopausal at least one year vs 47% of women postmenopausal at least 3 years. Thus, vaginal atrophy progressively worsens over time if untreated, resulting in decreased quality of life.
Spontaneously occurring hot flushes and sweating are prevalent symptoms experienced by women approximately a year prior to cessation of menstrual periods and herald imminent ovarian failure. Oldenhalve, et al found the incidence and severity of these symptoms to adversely affect quality of life with affected patients reporting a larger number of ancillary symptoms such as insomnia, fatigue, irritability and headaches. The symptoms of hot flashes and sweating have been the most frequently cited reasons by current hormone therapy users for initiation of therapy. Several RCT’s (randomized, controlled trials) consistently demonstrate the efficacy of estrogen preparations over placebo or botanicals for the treatment of these symptoms. Current recommendations are for short-term treatment with a dosage of estrogen that controls symptoms. For women with a uterus, the addition of progestogen prevents the endometrial hyperplasia, associated with unopposed estrogen use.(Grady D; RubinSM; Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Int Med 1992; 117:1016-1037) Recently, Hofling, et al have shown that the addition of testosterone, at physiologic levels of replacement, to estrogen and progestogen treatment in postmenopausal women counteracts the proliferative effects of estrogen/progestogen on human breast tissue. Although the use of testosterone after ovarian failure had previously been reserved for decreased sexual function or to augment osteoporosis treatment, there is accumulating evidence that it is the balance of androgens and estrogens after ovarian failure, which has important implications for modulating the risk of breast cancer.
In the wake of the WHI results, it certainly can be concluded that the use of Premarin™ and Provera™ in a population of women with a mean age of 63 has overall negative effects with an increased risk of breast cancer, cardio and cerebrovascular disease. However, subsequent subgroup analyses of the WHI population have shown a trend toward a protective effect of estrogen on younger women within 5 years of onset of menopause. (Manson JE; Allison MA, et al. Estrogen and coronary-artery calcification. N Engl J of Med. 2007; 356(25): 2591-602.) Furthermore, a French study by Scarabin, et al, showed that a the use of a bioidentical estrogen, 17 beta estradiol, administered transdermally rather than via the oral route was associated with a markedly reduced risk of venous thromboembolic episodes. Findings such as these illustrate the need to pursue the optimal types of ovarian hormones and routes by which they are administered in order to relieve symptoms and promote health for the long term.