Jesús González-Merlo

Skin collagen changes related to age and hormone replacement therapy

A total of 76 nulliparous women who had been hospitalized for minor operations, classified according to age group (by decade from 20s to 60s) and 118 postmenopausal women randomly allocated to one of four groups were studied. In all, 312 skin biopsies were taken from the lower abdomen at 0 and 12 months and the skin collagen changes noted. Collagen content decreased significantly with age beyond the 40s (P < 0.001) and after the menopause (P < 0.01). The decrease was preventable by the use of hormone replacement therapy. All the therapeutic regimens induced increases in skin collagen content, whereas in the control group a significant decrease was observed (P < 0.05).

Relationship between skin collagen and bone changes during aging.

There is evidence that skin collagen content and bone mass are influenced by estrogen deficiency, both of them declining in the years following menopause. The aim of our study was to analyze the relationship between changes in skin collagen content and bone mass during aging. A total of 76 nulliparous women who had been admitted for surgery of non-malignant processes were studied. All subjects were arranged into five age-groups (from 20 to 60 years). Bone mineral density was measured by dual photon absorptiometry and expressed in g/cm2 as the mean of the second to fourth lumbar vertebrae. Additionally, in all patients skin biopsies were taken from a non-sun exposed site in the lower abdomen (4 cm above the pubic symphysis) and osteocalcin levels were determined. Collagen decreased significantly with age after the 40s (P < 0.001) and after menopause (P < 0.001). Changes in bone mass were closely related to those detected in collagen (r = 0.586; P < 0.0001). In conclusion, our data suggest that bone mass and skin collagen decline in parallel with aging and that the hypoestrogenism developing in postmenopausal years has a significant effect on skin collagen content. Nevertheless, the question of whether osteoporosis is an intrinsic collagen disorder remains to be demonstrated.

The effect of hormone replacement therapy on postmenopausal bone loss

Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral.

Dehydrogesterone versus vaginal progesterone in the treatment of the endometrial luteal phase deficiency

Forty-four infertile patients with inadequate luteal phase histologically documented in at least two separate cycles and normal plasma levels of progesterone (P), estradiol (E2), and prolactin (PRL) were entered into treatment plans on a random basis involving at least 3 months of each of the following: P vaginal suppositories, dehydrogesterone, and no treatment. Success rates were similar for P (62.5%) and dehydrogesterone (68.7%), based on a corrected endometrial defect during the fourth treated cycle or when a term pregnancy was achieved. However, these figures are significantly different (P less than 0.001) when compared with 16.6% of the control group. In ten additional infertile patients with normal luteal function as assessed by endometrial histologic study and hormone measurements, a second biopsy was performed in a consecutive cycle under dehydrogesterone administration. In no case was the normal secretory pattern impaired. It is concluded that (1) both P and dehydrogesterone can be used to advantage in the treatment of luteal phase defects, and (2) therapy with dehydrogesterone does not alter the normal pattern of endometrial secretion.

The endometrial biopsy for diagnosis of luteal phase deficiency

We studied endometrial luteal phase in specimens from 660 biopsies done in 300 patients from our infertility clinic. A minimum of two (240 women) or three (60 women) endometrial biopsy specimens from separate cycles were taken regardless of the previous histologic findings in all patients. Statistical analysis of results by the McNemar and the Cochran Q tests for the significance of changes leads us to conclude that a minimum of two, and even three, endometrial biopsy specimens are needed for diagnosis of luteal phase deficiency.

Bone mineral density in surgically postmenopausal women receiving hormonal replacement therapy as assessed by dual photon absorptiometry

A total of 118 postmenopausal women who had undergone hysterectomy and bilateral oophorectomy were invited to participate in this study. Patients were randomly allocated to one of four study groups which received, respectively, conjugated equine oestrogens (CEE) 0.625 mg/day over a 25-day cycle each month (n = 28); transdermal 17 beta-oestradiol 50 micrograms/day over a 24-day cycle each month (n = 28), CEE 0.625 mg/day every day of the month (n = 32) and no treatment the control group (n = 30). All the treated patients also received 2.5 mg/day medroxyprogesterone acetate sequentially for the last 12 days of each cycle. Dual photon absorptiometry was performed before therapy commenced and repeated after 1 year in all four groups. The three therapeutic regimens induced increases in bone mass, whereas a significant decrease was observed in the control group (P < 0.05).

Effects of oophorectomy and hormone replacement therapy on pituitary-gonadal function

The purpose of this study was to determine how oophorectomy and different hormone replacement therapy (HRT) regimens using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day) influence the pituitary-gonadal axis function. Ninety (90) women, who had had regular menses prior to surgery, completed a 1-year follow-up period. Patients were assigned to 5 groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms day transdermal oestradiol (E2) cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These 3 groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day of MPA continuously, while the fifth (n = 19) constituted a control group. After oophorectomy all patients showed increases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and decreases in those of E2, oestrone (E1), prolactin (PRL), sex-hormone-binding globulin (SHBG), androstenedione (delta A4) and testosterone (T). No changes were detected in dehydroepiandrosterone sulphate (DHEA-S) levels. After HRT, decreases in FSH, LH and PRL levels and increases in those of E2, E1 and SHBG were observed, but no changes were seen in T, delta A4 or DHEA-S plasma levels. As the differences that were found cannot be attributed to the presence of ovaries, it is reasonable to assume that they were perhaps due to the treatment. All these changes, with the exception of a decrease in PRL levels, are therefore to be expected after HRT.

The Effect of Postovulatory Administration of Dehydrogesterone on Plasma Progesterone Levels

The effect of dehydrogesterone upon corpus luteum function as reflected by plasma progesterone levels was investigated in eight healthy women. No significant difference was found between control cycles and treated cycles when dehydrogesterone, 20 mg daily, was given orally for 10 days after ovulation.

Effects of oophorectomy and hormone replacement therapy on plasma lipids

The aim of this study was to determine the effects on plasma lipids and lipoproteins of oophorectomy and various hormone replacement therapy (HRT) delivery systems using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day). A total of 90 women completed the 1-year follow-up period. Patients were randomly assigned to five groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms/day transdermal oestradiol cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These three groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day MPA continuously, while the fifth (n = 19) constituted a treatment-free control group. After oophorectomy patients showed increases in low-density lipoprotein (LDL), apolipoprotein B and the atherogenic index, whereas after HRT patients exhibited falls in plasma LDL, apolipoprotein B and the atherogenic index and increases in high-density lipoprotein (HDL) and apolipoprotein A1. No significant changes in total cholesterol were observed after surgery or treatment and decreased levels of triglycerides were detected only in the transdermal treatment group.

Dehydrogesterone treatment of endometrial luteal phase deficiency after ovulation induced by clomiphene citrate and human chorionic gonadotropin

Twenty infertile patients being treated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) for induction of ovulation, with a defective endometrial secretory pattern despite normal plasma levels of progesterone, estradiol, and prolactin, were entered into treatment plans on a random basis involving the following: CC-hCG plus dehydrogesterone (group 1), and CC-hCG (group 2). Success rates were similar in both groups (20% and 30%, respectively), based on a corrected endometrial defect during the second treated cycle. It is concluded that progestational agents are of low therapeutic value in endometrial luteal phase deficiency induced by CC.