Use of Oral or Subcutaneous (pellet) Estradiol 17B with Natural Progesterone
in 200 Patients Followed for 10 years
Philip Warner, MD
201 "D" Street, Suite K
Marysville, CA 95901
MATERIALS AND METHODS
Two hundred patients from a private practice of OB/GYN were started on
hormonal replacement therapy for a variety of symptoms.
The patients presented with symptoms relating to ovarian hormone imbalance
or hormone deficiency and were all seen initially by the author. Many
of the patients were seen in consultation for hormonal problems after
having an evaluation elsewhere. The patients were seen at +1,3,6 month
intervals and then annual visits thereafter. At each visit, the women
were interviewed and questionnaires about symptoms or bleeding patterns
were completed. They had a complete physical examination and initial blood
work including FSH1 Blood Panel, Cholesterol, HDL and LDL. Mammograms
were obtained according to ACOG recommendations. Endometrial biopsies,
pelvic sonography, D&C, and hysteroscopy were accomplished as clinically
The patients were divided into two groups:
- Perimenopause (PEM) defined by irregular or excessive menstruation
or clinical symptoms and FSH> 15 IU/L.
- Postmenopause (POM) defined by natural or surgical absence of menses.
There were 73 (PEM) patients and 127 (POM) patients. Many of the (PEM)
patients might also be defined as having premenstrual syndrome. The
initial complaints of the (PEM) patients included dysfunctional uterine
bleeding, cyclic vascular headaches, anxiety, depression, insomnia,
diminished libido, breast tenderness, bloating and dysmenorrhea. The
(POM) patients symptoms included hot flashes, night sweats, vaginal
dryness, dysuria, dysparuenia, diminished libido, depression, memory
loss and insomnia.
The patients in Group 1 (PEM) received sequential estradiol [E2] and
progesterone [P] therapy, while Group 2 (POM) received combined E2 &
P therapy. A subgroup of (POM) patients who did not respond to oral therapy
satisfactorily were placed on subcutaneous (pellet) implants. Of these
patients, those with an intact uterus received oral micronized progesterone
daily, while those with surgical menopause and no uterus received only
the estradiol implants. In some cases, estradiol and testosterone implants
The hormones in Group 1 (PEM) patients were micronized estradiol 17B
USP 0.5 mgm mixed with alpha lactose in gelatin capsules (Bajamar Labs,
St. Louis, MO) taken 25 days a month with micronized USP progesterone
100 mgm in gelatin capsules (Bajamar Labs, St. Louis, MO) taken BID, 14
days per month.
The hormones in Group 2 (POM) patients were micronized estradiol 17B
0.35 mgm and micronized progesterone 100 mgm both in a single capsule
taken daily. In some cases the dose was increased to one capsule BID.
The implants were 25 mgm estradiol pellets, average 2 pellets and 75 mgm
testosterone proprionate pellet. (College Pharmacy, Colorado Springs,
Table 1 Hormone Replacement Therapy: (PEM) Patients
E2 25 days/month P 14 days/month N=73
|Dysfunctional Uterine Bleeding
|Cyclic Vascular Headaches
Table 2 Hormone Replacement Therapy: (POM) Patients
E2 & P combined in One Capsule Daily* N=127
| Vaginal Dryness
|Uterine Bleeding or Spotting
Thirty-two of the original two hundred patients are no longer being seen
due to death, moving away from the area, or dissatisfaction with treatment.
The remaining patients are continuing follow-up visits. The group 1 (PEM)
patients who initially showed dysfunctional uterine bleeding patterns
reverted to normal patterns in 75% of the cases. However, this is modified
by the fact that some of the persistent cases subsequently underwent hysterectomy
or endometrial ablation. Additionally, at an average age of 50, the (PEM)
patients were successfully convened to (POM) patients by switching to
a combined E2 & P regimen. It generally took 6 months after switching
regimens for the amenorrheic pattern to occur.
In Table I the number of patients with residual symptoms at varying intervals
of time are listed. Within one year, these patients showed regulation
of their menstrual pattern and significant decrease in the symptoms associated
with premenstrual syndrome. Those patient% continuing with significant
hyper or polymenorrhea eventually came to hysterectomy or endometrial
ablation. The menstrual flow pattern decreased the longer the patient
was on sequential hormone therapy. When the patients were switched to
a combined regimen, they eventually became amenorrheic. In some cases
the decision to switch therapy was dictated by failure of withdrawal bleeding
after 1 to 2 months of progesterone only therapy. This can be an indicator
to convert a (PEM) patient to a (PONI) patient instead of an arbitrary
age of 50.
In table 2, the (POM) patients showed excellent relief of hypoestrogenic
symptoms on the combined regimen. In addition, compliance was aided by
the necessity of taking only one capsule per day containing both E2 &
P. The patients were especially satisfied by having no sporadic bleeding
or spotting while obtaining benefits of estrogen therapy. Forty-two patients
continued to complain of some hypoestrogenic symptoms and were given estradiol
(and in some cases testosterone) pellets. This mode of treatment is very
effective in this select group of patients. The use of hormone implants
was initiated by Dr. Robert Greenblatt in the 1930s. It provides a constant
hormone release and stable blood level for the patient who otherwise is
unable to achieve relief of symptoms by the oral or transdermal (patch)
The perimenopausal patient with her associated symptoms of abnormal bleeding
patterns, premenstrual syndrome, and vascular headaches can benefit from
hormone balance therapy. The use of sequential estradiol 17B with oral
micronized progesterone offers an excellent method of therapy. It does
not appear advantageous to substitute progestogens which while effective
can "muddy the water" by aggravating symptoms of breast tenderness,
depression, bloating etc. - the very symptoms we are trying to relieve.
The postmenopausal patient benefits from combined estradiol and micronized
progesterone therapy without the continued bleeding pattern associated
with the use of medroxyprogesterone. The progesterone also does not alter
the favorable changes in lipoproteins induced by estrogen. In addition,
compliance is aided by the two hormones together in one capsule being
ingested once per day.
It remains to be proven if the protection in the long term against osteoporosis
and cardiovascular disease will remain the same with these agents. However,
low dose micronized 17B estradiol has been shown to prevent bone loss
in postmenopause women and micronized oral progesterone has been shown
to be active in bone metabolism altering bone turnover and acting directly
on the osteoblast to promote bone formation.
Finally, alternative routes of therapy must be utilized in individual
patients for whom oral therapy is not successful. Subcutaneous (pellet)
implants are an effective, simple method to be utilized when necessary.
Please refer any inquires to:
Phillip 0. Warner, M.D.
Menopause Institute of Northern California
700 W. Parr Ave., Suite D
Los Gatos, CA 95030
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