A group of infertility patients were evaluated by an endometrial biopsy, timed with a basal body temperature chart, serum luteinizing hormone radioimmunassay to pinpoint ovulation, and daily serum progesterone values during a control and a treatment cycle. Progesterone in the suppository or intramuscular form and 17-hydroxyprogesterone caproate* were administered during the luteal phase to a group of volunteer patients with normal corpus luteum function to determine if these compounds would depress serum progesterone levels as do certain progestational agents. There was no apparent inhibition of corpus luteum function as no decrease in progesterone production occurred. Despite the additive effect of progesterone administration demonstrated by elevated serum levels, endometrial biopsies remained in phase when dated from the estimated day of ovulation.
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PMID 4812567 4812567 DOI 10.1016/s0002-9378(16)33685-7 10.1016/s0002-9378(16)33685-7 Aksel et al. 1974, Aksel 1974
Cite this article
Aksel, S., & Jones, G. S. (1974). Effect of progesterone and 17-hydroxyprogesterone caproate on normal corpus luteum function. American journal of obstetrics and gynecology, 118(4), 466-472. https://doi.org/10.1016/s0002-9378(16)33685-7
Aksel S, Jones GS. Effect of progesterone and 17-hydroxyprogesterone caproate on normal corpus luteum function. Am J Obstet Gynecol. 1974;118(4):466-472. doi:10.1016/s0002-9378(16)33685-7
Aksel, S., and G. S. Jones. "Effect of progesterone and 17-hydroxyprogesterone caproate on normal corpus luteum function." American journal of obstetrics and gynecology, vol. 118, no. 4, 1974, pp. 466-472.
Tamoxifen at a dose of 10 mg/day for 5 days was given to five infertile women in the luteal phase. Daily serum samples were obtained during the luteal phase for radioimmunoassay of progesterone (P), estradiol (E2), follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. The integrated luteal phase concentrations of serum P and E2 before and after cycles of tamoxifen treatment increased from 87.8 +/- 16.2 ng/ml and 1120 +/- 164.4 pg/ml to 131.6 +/- 18.9 ng/ml and 1461 +/- 205.2 pg/ml, respectively (P less than 0.01 and P less than 0.05). No apparent increase in circulating LH levels was seen in one of the five cases, but this patient's serum P and E2 levels rose nonetheless. This suggests that the significant increase in circulating P and E2 induced by tamoxifen is not consistently associated with an increase in serum LH concentration.
The null hypothesis of this study is that the patterns of steroid secretion exhibited by the human corpus luteum in response to exogenous human chorionic gonadotropin stimulation are independent of corpus luteum age at the time of treatment. Twenty-five normally cycling women in whom the midcycle urinary luteinizing hormone surge (luteal day 0) was identified and from whom blood samples were obtained daily from cycle day 11 until menses were prospectively randomized to receive no treatment (group I, n = 5) or exogenous human chorionic gonadotropin 5000 IU administered intramuscularly on luteal day 0 (group II, n = 5), +4 (group III, n = 5), +8 (group IV, n = 5), or +12 (group V, n = 5). Serum concentrations of estrone, estradiol, progesterone, 17-hydroxyprogesterone, and androstenedione were measured by specific radioimmunoassays in all subjects; serum human chorionic gonadotropin concentrations were determined by immunoradiometric assay in treated subjects. Serum human chorionic gonadotropin levels (mean +/- SEM) were virtually identical among treatment groups (p greater than 0.05). Luteal phase duration (mean +/- SEM) was prolonged (p less than 0.05) only in group V (18.4 +/- 0.5 days) compared with untreated subjects (group I 13.8 +/- 0.7 days). In all groups estrone and 17-hydroxyprogesterone concentrations closely paralleled those of estradiol and progesterone, respectively. Steroid data and progesterone/estradiol ratios (mean +/- SEM) in groups I and II were indistinguishable and were combined (control, n = 10). Group III subjects exhibited patterns of steroid secretion similar to groups I and II, although progesterone was moderately increased after human chorionic gonadotropin treatment. In groups IV and V, progesterone increased (p less than 0.05) 1 day after human chorionic gonadotropin and remained elevated for 5 to 6 days; a 4-day rise (p less than 0.05) in estradiol began 3 days after treatment, and androstenedione rose modestly in parallel. Progesterone/estradiol ratios in groups III through V increased (p less than 0.05) approximately twofold after human chorionic gonadotropin treatment and remained elevated for 4 to 5 days. The human corpus luteum exhibits distinct age-dependent patterns of steroid secretion in response to exogenous human chorionic gonadotropin stimulation, an observation that may have clinical implications regarding the empirical use of exogenous human chorionic gonadotropin in support of luteal function.
The corpus luteum is a vital yet temporary organ that plays a crucial role in fertility during the luteal phase. An endocrine structure in females exists within the ovary once the ovarian follicle releases a mature ovum during ovulation. See Image. Anatomy of the Internal Structures of the Ovary. The secretion of hormones from the corpus luteum stops within 14 days after ovulation if the oocyte is not fertilized. It then degenerates into a scar within the ovary, known as corpus albicans. The corpus luteum's role is to maintain a uterine environment that allows for implementation and pregnancy. This occurs by the release of pregnancy-related hormones and regulation of the hypothalamic-pituitary access through inhibition of gonadotropin-releasing hormone from the hypothalamus, which in turn decreases the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) released from the anterior pituitary. The primary hormone produced by the corpus luteum is progesterone, but it also produces inhibin A and estradiol. In the absence of fertilization, the corpus luteum regresses over time. A corpus luteum develops each time a woman ovulates so that she produces a corpus luteum numerous times throughout her lifetime.
Menstruation has many of the features of an inflammatory process. The complexity and sequence of inflammatory-type events leading to the final tissue breakdown and bleeding are slowly being unravelled. Progesterone has anti-inflammatory properties, and its rapidly declining levels (along with those of estrogen) in the late secretory phase of each non-conception cycle, initiates a sequence of interdependent events of an inflammatory nature involving local inter-cellular interactions within the endometrium. Intracellular responses to loss of progesterone (in decidualized stromal, vascular and epithelial cells) lead to decreased prostaglandin metabolism and loss of protection from reactive oxygen species (ROS). Increased ROS results in release of NFκB from suppression with activation of target gene transcription and increased synthesis of pro-inflammatory prostaglandins, cytokines, chemokines and matrix metalloproteinases (MMP). The resultant leukocyte recruitment, with changing phenotypes and activation, provide further degradative enzymes and MMP activators, which together with a hypoxic environment induced by prostaglandin actions, lead to the tissue breakdown and bleeding characteristic of menstruation. In parallel, at sites where shedding is complete, microenvironmentally-induced changes in phenotypes of neutrophils and macrophages from proto anti-inflammatory, in addition to induction of growth factors, contribute to the very rapid re-epithelialization and restoration of tissue integrity.