It has been suggested by some that the absence of significant effect in some of these studies could be due to selective prescription to overweight women who have higher baseline estrone, or to the very low progesterone serum levels after oral administration leading to a high tumor inactivation rate.Evaluating the response of breast tissue density to HRT using mammography appears to help assessing the degree of breast cancer risk associated with therapy; women with dense or mixed-dense breast tissue have a higher risk of developing breast cancer than those with low density tissue.Micronized progesterone does not appear to be associated with breast cancer risk when used for less than five years with limited data suggesting an increased risk when used for longer duration.A retrospective Cox proportional hazards analysis from Richard Neapolitan endorsed the reduced risk breast cancer with conjugated equine estrogen usage alone, but also suggested that conjugated equine estrogen with medroxyprogesterone acetate was associated with a risk reduction in breast cancer and that bioidentical hormone therapy was not associated with a statistically significant effect. There have been no prospective randomized clinical trials comparing the two routes of administration with regards to breast cancer.For women who previously have had breast cancer, it is recommended to first consider other options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, cholesterol-lowering agents and aspirin for cardiovascular disease, and vaginal estrogen for local symptoms. Observational studies of systemic HRT after breast cancer are generally reassuring.
Pathophysiology
The GNAS1 gene involved in both Pseudohypoparathyroidism type 1a and Pseudopseudohypoparathyroidism is greatly affected by imprinting. When a father who has Pseudohypoparathyroidism undergoes spermatogenesis, imprinting of the GNAS1 gene inactivates both copies of his genes: one will be Functional and the other will be defective. Tissues in the body will re-activate different copies of the GNAS1 gene selectively; the kidneys will selectively activate the (functional) maternal copy while keeping the (defective) paternally-derived gene imprinted and inactive, even in normal individuals. Since the maternally-derived GNAS1 gene is functional, renal handling of calcium and phosphate is normal, and homeostasis is maintained in Pseudopseudohypoparathyroidism. However, the rest of the tissues will instead selectively display the defective gene, resulting in haploinsufficiency of the GNAS1 product in most tissues, and giving the phenotype of Pseudohypoparathyroidism type 1a. As a result, there is also a normal response of urinary cAMP to PTH, and normal serum PTH. Diagnosis
The diagnosis is based on the presence of the Albright hereditary osteodystrophy pseudotype but without the PTH resistance. Blood tests including calcium, phosphate, and PTH will exclude other forms of Pseudohypoparathyroidism. X-rays may reveal a short fourth metacarpal. Genetic testing can confirm the diagnosis by showing GNAS gene mutation. Treatment
Treatments focuses on symptoms, with genetic counseling recommended. History
It was characterized in 1952 by Fuller Albright as "pseudo-pseudohypoparathyroidism" (with hyphen). See also
Antidisestablishmentarianism
Floccinaucinihilipilification
GNAS complex locus
Honorificabilitudinitatibus
Longest word in English
Longest words
Parathyroid hormone
Pneumonoultramicroscopicsilicovolcanoconiosis
Supercalifragilisticexpialidocious

References


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